@article{boston_wang_xi_kim_fellner_scott_ziegler_van landeghem_blikslager_odle_2023, title={Effects of Prebiotic Galactooligosaccharide (GOS) on Hindgut Microbial Composition of Pigs During the Peri-Weaning Period}, volume={101}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skad281.228}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Boston, Timothy E. and Wang, Feng and Xi, Lin and Kim, Sung Woo and Fellner, Vivek and Scott, Mark F. and Ziegler, Amanda L. and Van Landeghem, Laurianne and Blikslager, Anthony T. and Odle, Jack}, year={2023}, month={Nov}, pages={187–188} }
 @article{boston_wang_xi_kim_fellner_scott_ziegler_van landeghem_blikslager_odle_2023, title={Effects of Prebiotic Galactooligosaccharide (Gos) on Piglet Growth and Jejunal Morphology During the Peri-Weaning Period}, volume={101}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skad341.313}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Boston, Timothy E. and Wang, Feng and Xi, Lin and Kim, Sung Woo and Fellner, Vivek and Scott, Mark F. and Ziegler, Amanda L. and Van Landeghem, Laurianne and Blikslager, Anthony T. and Odle, Jack}, year={2023}, month={Oct}, pages={276–277} }
 @article{mariant_bacola_van landeghem_2023, title={Mini-Review: Enteric glia of the tumor microenvironment: An affair of corruption}, volume={814}, ISSN={["1872-7972"]}, DOI={10.1016/j.neulet.2023.137416}, abstractNote={The tumor microenvironment corresponds to a complex mixture of bioactive products released by local and recruited cells whose normal functions have been “corrupted” by cues originating from the tumor, mostly to favor cancer growth, dissemination and resistance to therapies. While the immune and the mesenchymal cellular components of the tumor microenvironment in colon cancer have been under intense scrutiny over the last two decades, the influence of the resident neural cells of the gut on colon carcinogenesis has only very recently begun to draw attention. The vast majority of the resident neural cells of the gastrointestinal tract belong to the enteric nervous system and correspond to enteric neurons and enteric glial cells, both of which have been understudied in the context of colon cancer development and progression. In this review, we especially discuss available evidence on enteric glia impact on colon carcinogenesis. To highlight “corrupted” functioning in enteric glial cells of the tumor microenvironment and its repercussion on tumorigenesis, we first review the main regulatory effects of enteric glial cells on the intestinal epithelium in homeostatic conditions and we next present current knowledge on enteric glia influence on colon tumorigenesis. We particularly examine how enteric glial cell heterogeneity and plasticity require further appreciation to better understand the distinct regulatory interactions enteric glial cell subtypes engage with the various cell types of the tumor, and to identify novel biological targets to block enteric glia pro-carcinogenic signaling.}, journal={NEUROSCIENCE LETTERS}, author={Mariant, Chloe L. and Bacola, Gregory and Van Landeghem, Laurianne}, year={2023}, month={Sep} }
 @article{vales_bacola_biraud_bessard_geraldo_dougherty_lashani_bossard_flamant_duchalais_et al._2023, title={Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesis (vol 49, pg 172, 2019)}, volume={88}, ISSN={["2352-3964"]}, DOI={10.1016/j.ebiom.2023.104448}, abstractNote={The publisher regrets that due to a production error, supplemental figures were accidentally omitted from the published version of this research paper. The original article has been updated. The publisher would like to apologise for any inconvenience caused. Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesisAltogether, our results show that EGCs, once activated by the tumor, acquire a pro-tumorigenic phenotype and stimulate CSC-driven tumorigenesis via a PGE2/EP4/EGFR-dependent pathway. Full-Text PDF Open Access}, journal={EBIOMEDICINE}, author={Vales, Simon and Bacola, Gregory and Biraud, Mandy and Bessard, Anne and Geraldo, Fanny and Dougherty, Kelsie A. and Lashani, Shaian and Bossard, Celine and Flamant, Mathurin and Duchalais, Emilie and et al.}, year={2023}, month={Feb} }
 @article{francois_thedrez_garcon_ayer_sotin_dijk_blanchard_chadeuf_arnaud_croyal_et al._2021, title={PCSK9 is not secreted from mature differentiated intestinal cells}, volume={62}, ISSN={["1539-7262"]}, DOI={10.1016/j.jlr.2021.100096}, abstractNote={Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes lysosomal degradation of the LDL receptor and is a key regulator of cholesterol metabolism. After the liver, the small intestine is the second organ that highly expresses PCSK9. However, the small intestine's ability to secrete PCSK9 remains a matter of debate. While liver-specific PCSK9-deficient mice present no PCSK9 in systemic blood, human intestinal Caco-2 cells can actively secrete PCSK9. This raises the possibility for active intestinal secretion via the portal blood. Here, we aimed to determine whether enterocytes can secrete PCSK9 using in vitro, ex vivo, and in vivo approaches. We first observed that PCSK9 secretion from Caco-2 cells was biphasic and dependent on Caco-2 maturation status. Transcriptional analysis suggested that this transient reduction in PCSK9 secretion might be due to loss of SREBP2-mediated transcription of PCSK9. Consistently, PCSK9 secretion was not detected ex vivo in human or mouse intestinal biopsies mounted in Ussing chambers. Finally, direct comparison of systemic versus portal blood PCSK9 concentrations in WT or liver-specific PCSK9-deficient mice confirmed the inability of the small intestine to secrete PCSK9 into the portal compartment. Altogether, our data demonstrate that mature enterocytes do not secrete PCSK9 and reinforce the central role of the liver in the regulation of the concentration of circulating PCSK9 and consequently of cellular LDL receptors.}, journal={JOURNAL OF LIPID RESEARCH}, author={Francois, Moreau and Thedrez, Aurelie and Garcon, Damien and Ayer, Audrey and Sotin, Thibaud and Dijk, Wieneke and Blanchard, Claire and Chadeuf, Gilliane and Arnaud, Lucie and Croyal, Mikael and et al.}, year={2021} }
 @article{sheridan_pridgen_odle_van landeghem_blikslager_ziegler_2020, title={A Glial Cell Inhibitor Blocks Epithelial Barrier Repair in a Pig Model of Intestinal Ischemia}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.02030}, abstractNote={The gut epithelium functions as a barrier against toxic luminal contents which can repair efficiently after injury to prevent systemic illness and death. However, we have shown that repair is severely hindered in neonates as compared to juveniles in our translational pig model of intestinal ischemia. The subepithelial enteric glial cell (EGC) network is known to promote epithelial repair by paracrine signaling mechanisms. This EGC network develops postnatally; therefore, we believe this repair defect in neonates is due to an underdeveloped EGC network. In support of this, we hypothesize that EGC inhibition in juveniles will block epithelial barrier repair after ischemic injury mimicking the neonatal phenotype. Ischemia‐injured jejunum of juvenile pigs was recovered ex vivo with and without fluoroacetate (FA), a glial inhibitor. Transepithelial electrical resistance (TEER) was monitored as a measure of barrier function, and tissues were collected for imaging analysis and primary EGC culture. FA inhibited TEER recovery at all tested concentrations (P<0.0001). Histology showed 500μM FA optimally inhibits epithelial repair (P=0.0196) without directly damaging the epithelium (P=0.5509). Cellular metabolism marker c‐fos has been optimized for immunofluorescence in control tissues and ongoing imaging work will validate selective inhibition of EGC metabolism by 500μM FA. In addition, pig EGC isolation and culture has been optimized, so that future work will confirm inhibitory effects of FA on EGC signaling functions in vitro. Understanding the development of glial‐epithelial crosstalk in barrier repair will ultimately guide novel clinical solutions to improve outcomes in neonatal patients affected by intestinal injury.}, number={S1}, journal={FASEB JOURNAL}, publisher={Wiley}, author={Sheridan, Ana and Pridgen, Tiffany and Odle, Jack and Van Landeghem, Laurianne and Blikslager, Anthony and Ziegler, Amanda}, year={2020}, month={Apr} }
 @article{shapiro_ziegler_odle_van landeghem_blikslager_2020, title={Effects of Oligosaccharide Supplementation on Intestinal Morphology and Enteric Glial Cell Marker Expression in a Neonatal Pig Model}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.09457}, abstractNote={We have shown that oligosaccharide supplementation can modulate the gut flora in neonates, and the microbiome is known to drive the maturation of the enteric glial cell (EGC) network postnatally. Here, we test the effects of dietary oligosaccharides on postnatal changes in the EGC network and intestinal morphology in a neonatal pig model.After suckling colostrum for 24‐hours, one‐day‐old pigs were grouped onto one of three formula‐based diets: control, high oligosaccharide (1:1 mixture of galactooligosaccharide and polydextrose, 8g/L), or low oligosaccharide (4g/L). Small intestine and colon samples were collected at 1‐ 7‐ 14‐ and 21‐ days‐of‐age for western blot and histological analysis. Preliminary histological results indicate a trend toward a decreased small intestinal villus length in the high oligosaccharide group at 7‐days‐of‐age, indicative of accelerated intestinal maturity. Expression of the EGC marker glial fibrillary acidic protein is increased in the small intestinal mucosa at 7‐ and 14‐days‐of‐age in the high oligosaccharide group based on a preliminary western blot (n=1). Following ongoing work to assess crypt morphology and quantify additional EGC markers S100B, PLP‐1, Sox10 in the small intestine and colon, we expect to find increased mucosal expression of EGC markers earlier in postnatal development in the high oligosaccharide group, as well as histological changes consistent with enhanced rates of gut maturation in pigs fed a high oligosaccharide diet. Understanding how dietary inputs drive intestinal development postnatally may improve practices for managing optimal gut heath early in life.}, number={S1}, journal={FASEB JOURNAL}, publisher={Wiley}, author={Shapiro, Lindsey and Ziegler, Amanda and Odle, Jack and Van Landeghem, Laurianne and Blikslager, Anthony}, year={2020}, month={Apr} }
 @article{erwin_touvron_odle_van landeghem_blikslager_ziegler_2020, title={iDISCO Allows Complete Visualization and Analysis of Postnatal Enteric Nervous System Development in a Comparative Pig Model}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.03991}, abstractNote={The enteric nervous system consists of a dense, complex network of neurons and glia which are instrumental in the maturation of normal intestinal physiology after birth. Our lab uses a comparative pig model to study the postnatal development of the enteric glial network and its role in regulating intestinal barrier functions in neonates. Immunolabeling‐enabled three‐dimensional (3D) imaging of solvent‐cleared organs (iDISCO) is a method of preparing tissue samples for volume imaging with a light sheet microscope. iDISCO has been optimized for use in primarily mouse organs and embryos for the study of early development and offers a more complete picture of the tissue than traditional histological analysis. Our objective was to optimize the iDISCO protocol for use in porcine intestinal tissue to allow complete qualitative and quantitative analysis of postnatal development of the enteric glial network in our comparative pig model. Antibodies against glial cell markers S100b, Sox10, and glial fibrillary acidic protein (GFAP) were used to triple‐stain fixed full‐thickness 3mm by 5mm samples of porcine jejunum using the iDISCO protocol. Samples were imaged with a light‐sheet microscope (Ultra‐II, LaVision BioTec®) using three different fluorescent channels and datasets were visualized and analyzed in 3D with Imaris software (Oxford Instruments®). The percent volume of GFAP+ glial cells was quantified by manually masking individual intestinal villi and optimizing a surface algorithm to identify glial network structures within those villi. Antibodies against all three markers tested produced the predicted staining pattern with minimal non‐specific staining. Percent of jejunal villus volume occupied by GFAP+ glia is higher in 6‐week‐old versus 2‐week‐old pig (0.49% versus 0.23%, *P≤0.05). Ongoing work will optimize quantification techniques for S100b and Sox10, and assess co‐localization patterns of these glial markers in the jejunum at discrete timepoints postnatally. iDISCO is a powerful imaging modality which will allow our lab to directly assess the expansion, complexity, and localization of glial cell subtypes by marker co‐expression analysis at discrete postnatal timepoints, and will be utilized in future studies to explore effects of disease and external interventions on the enteric glial network.}, number={S1}, journal={FASEB JOURNAL}, publisher={Wiley}, author={Erwin, Sara and Touvron, Melissa and Odle, Jack and Van Landeghem, Laurianne and Blikslager, Anthony and Ziegler, Amanda}, year={2020}, month={Apr} }
 @article{aureille_buffiere-ribot_harvey_boyault_pernet_andersen_bacola_balland_fraboulet_van landeghem_et al._2019, title={Nuclear envelope deformation controls cell cycle progression in response to mechanical force}, volume={20}, ISSN={["1469-3178"]}, DOI={10.15252/embr.201948084}, abstractNote={The shape of the cell nucleus can vary considerably during developmental and pathological processes; however, the impact of nuclear morphology on cell behavior is not known. Here, we observed that the nuclear envelope flattens as cells transit from G1 to S phase and inhibition of myosin II prevents nuclear flattening and impedes progression to S phase. Strikingly, we show that applying compressive force on the nucleus in the absence of myosin II‐mediated tension is sufficient to restore G1 to S transition. Using a combination of tools to manipulate nuclear morphology, we observed that nuclear flattening activates a subset of transcription factors, including TEAD and AP1, leading to transcriptional induction of target genes that promote G1 to S transition. In addition, we found that nuclear flattening mediates TEAD and AP1 activation in response to ROCK‐generated contractility or cell spreading. Our results reveal that the nuclear envelope can operate as a mechanical sensor whose deformation controls cell growth in response to tension.}, number={9}, journal={EMBO REPORTS}, author={Aureille, Julien and Buffiere-Ribot, Valentin and Harvey, Ben E. and Boyault, Cyril and Pernet, Lydia and Andersen, Tomas and Bacola, Gregory and Balland, Martial and Fraboulet, Sandrine and Van Landeghem, Laurianne and et al.}, year={2019}, month={Sep} }
 @article{duchalais_guilluy_nedellec_touvron_bessard_touchefeu_bossard_boudin_louarn_neunlist_et al._2018, title={Colorectal Cancer Cells Adhere to and Migrate Along the Neurons of the Enteric Nervous System}, volume={5}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/J.JCMGH.2017.10.002}, DOI={10.1016/J.JCMGH.2017.10.002}, abstractNote={Background & AimsIn several types of cancers, tumor cells invade adjacent tissues by migrating along the resident nerves of the tumor microenvironment. This process, called perineural invasion, typically occurs along extrinsic nerves, with Schwann cells providing physical guidance for the tumor cells. However, in the colorectal cancer microenvironment, the most abundant nervous structures belong to the nonmyelinated intrinsic enteric nervous system (ENS). In this study, we investigated whether colon cancer cells interact with the ENS.MethodsTumor epithelial cells (TECs) from human primary colon adenocarcinomas and cell lines were cocultured with primary cultures of ENS and cultures of human ENS plexus explants. By combining confocal and atomic force microscopy, as well as video microscopy, we assessed tumor cell adhesion and migration on the ENS. We identified the adhesion proteins involved using a proteomics approach based on biotin/streptavidin interaction, and their implication was confirmed further using selective blocking antibodies.ResultsTEC adhered preferentially and with stronger adhesion forces to enteric nervous structures than to mesenchymal cells. TEC adhesion to ENS involved direct interactions with enteric neurons. Enteric neuron removal from ENS cultures led to a significant decrease in tumor cell adhesion. TECs migrated significantly longer and further when adherent on ENS compared with on mesenchymal cells, and their trajectory faithfully followed ENS structures. Blocking N-cadherin and L1CAM decreased TEC migration along ENS structures.ConclusionsOur data show that the enteric neuronal network guides tumor cell migration, partly via L1CAM and N-cadherin. These results open a new avenue of research on the underlying mechanisms and consequences of perineural invasion in colorectal cancer. In several types of cancers, tumor cells invade adjacent tissues by migrating along the resident nerves of the tumor microenvironment. This process, called perineural invasion, typically occurs along extrinsic nerves, with Schwann cells providing physical guidance for the tumor cells. However, in the colorectal cancer microenvironment, the most abundant nervous structures belong to the nonmyelinated intrinsic enteric nervous system (ENS). In this study, we investigated whether colon cancer cells interact with the ENS. Tumor epithelial cells (TECs) from human primary colon adenocarcinomas and cell lines were cocultured with primary cultures of ENS and cultures of human ENS plexus explants. By combining confocal and atomic force microscopy, as well as video microscopy, we assessed tumor cell adhesion and migration on the ENS. We identified the adhesion proteins involved using a proteomics approach based on biotin/streptavidin interaction, and their implication was confirmed further using selective blocking antibodies. TEC adhered preferentially and with stronger adhesion forces to enteric nervous structures than to mesenchymal cells. TEC adhesion to ENS involved direct interactions with enteric neurons. Enteric neuron removal from ENS cultures led to a significant decrease in tumor cell adhesion. TECs migrated significantly longer and further when adherent on ENS compared with on mesenchymal cells, and their trajectory faithfully followed ENS structures. Blocking N-cadherin and L1CAM decreased TEC migration along ENS structures. Our data show that the enteric neuronal network guides tumor cell migration, partly via L1CAM and N-cadherin. These results open a new avenue of research on the underlying mechanisms and consequences of perineural invasion in colorectal cancer.}, number={1}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Duchalais, Emilie and Guilluy, Christophe and Nedellec, Steven and Touvron, Melissa and Bessard, Anne and Touchefeu, Yann and Bossard, Céline and Boudin, Hélène and Louarn, Guy and Neunlist, Michel and et al.}, year={2018}, pages={31–49} }
 @article{vales_touvron_van landeghem_2018, title={Enteric glia: Diversity or plasticity?}, volume={1693}, ISSN={["1872-6240"]}, DOI={10.1016/j.brainres.2018.02.001}, abstractNote={Glial cells of the enteric nervous system correspond to a unique glial lineage distinct from other central and peripheral glia, and form a vast and abundant network spreading throughout all the layers of the gastrointestinal wall. Research over the last two decades has demonstrated that enteric glia regulates all major gastrointestinal functions via multiple bi-directional crosstalk with enteric neurons and other neighboring cell types. Recent studies propose that enteric glia represents a heterogeneous population associated with distinct localization within the gut wall, phenotype and activity. Compelling evidence also indicates that enteric glial cells are capable of plasticity leading to phenotypic changes whose pinnacle so far has been shown to be the generation of enteric neurons. While alterations of the glial network have been heavily incriminated in the development of gastrointestinal pathologies, enteric glial cells have also recently emerged as an active player in gut-brain signaling. Therefore, the development of tools and techniques to better appraise enteric glia heterogeneity and plasticity will undoubtedly unveil critical regulatory mechanisms implicated in gut health and disease, as well as disorders of the gut-brain axis.}, journal={BRAIN RESEARCH}, author={Vales, Simon and Touvron, Melissa and Van Landeghem, Laurianne}, year={2018}, month={Aug}, pages={140–145} }
 @article{ziegler_pridgen_mills_gonzalez_van landeghem_odle_blikslager_2018, title={Epithelial restitution defect in neonatal jejunum is rescued by juvenile mucosal homogenate in a pig model of intestinal ischemic injury and repair}, volume={13}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0200674}, DOI={10.1371/journal.pone.0200674}, abstractNote={Intestinal ischemic injury results sloughing of the mucosal epithelium leading to host sepsis and death unless the mucosal barrier is rapidly restored. Neonatal necrotizing enterocolitis (NEC) and volvulus in infants is associated with intestinal ischemia, sepsis and high mortality rates. We have characterized intestinal ischemia/ repair using a highly translatable porcine model in which juvenile (6-8-week-old) pigs completely and efficiently restore barrier function by way of rapid epithelial restitution and tight junction re-assembly. In contrast, separate studies showed that younger neonatal (2-week-old) pigs exhibited less robust recovery of barrier function, which may model an important cause of high mortality rates in human infants with ischemic intestinal disease. Therefore, we aimed to further refine our repair model and characterize defects in neonatal barrier repair. Here we examine the defect in neonatal mucosal repair that we hypothesize is associated with hypomaturity of the epithelial and subepithelial compartments. Following jejunal ischemia in neonatal and juvenile pigs, injured mucosa was stripped from seromuscular layers and recovered ex vivo while monitoring transepithelial electrical resistance (TEER) and 3H-mannitol flux as measures of barrier function. While ischemia-injured juvenile mucosa restored TEER above control levels, reduced flux over the recovery period and showed 93±4.7% wound closure, neonates exhibited no change in TEER, increased flux, and a 11±23.3% increase in epithelial wound size. Scanning electron microscopy revealed enterocytes at the wound margins of neonates failed to assume the restituting phenotype seen in restituting enterocytes of juveniles. To attempt rescue of injured neonatal mucosa, neonatal experiments were repeated with the addition of exogenous prostaglandins during ex vivo recovery, ex vivo recovery with full thickness intestine, in vivo recovery and direct application of injured mucosal homogenate from neonates or juveniles. Neither exogenous prostaglandins, intact seromuscular intestinal layers, nor in vivo recovery enhanced TEER or restitution in ischemia-injured neonatal mucosa. However, ex vivo exogenous application of injured juvenile mucosal homogenate produced a significant increase in TEER and enhanced histological restitution to 80±4.4% epithelial coveragein injured neonatal mucosa. Thus, neonatal mucosal repair can be rescued through direct contact with the cellular and non-cellular milieu of ischemia-injured mucosa from juvenile pigs. These findings support the hypothesis that a defect in mucosal repair in neonates is due to immature repair mechanisms within the mucosal compartment. Future studies to identify and rescue specific defects in neonatal intestinal repair mechanisms will drive development of novel clinical interventions to reduce mortality in infants affected by intestinal ischemic injury.}, number={8}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Ziegler, Amanda L. and Pridgen, Tiffany A. and Mills, Juliana K. and Gonzalez, Liara M. and Van Landeghem, Laurianne and Odle, Jack and Blikslager, Anthony T.}, editor={Karhausen, JörnEditor}, year={2018}, month={Aug}, pages={e0200674} }
 @article{chatterji_hamilton_liang_andres_wijeratne_mizuno_simon_hicks_foley_pitarresi_et al._2018, title={Sa1664 - The Lin28B-Imp1 Axis Directs a Post-Transcriptional Regulon of Oncogenic Signaling in the Intestine}, volume={154}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(18)31488-4}, DOI={10.1016/S0016-5085(18)31488-4}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Chatterji, Priya and Hamilton, Kathryn E. and Liang, Shun and Andres, Sarah F. and Wijeratne, H.R. Sagara and Mizuno, Rei and Simon, Lauren and Hicks, Philip D. and Foley, Shawn and Pitarresi, Jason and et al.}, year={2018}, month={May}, pages={S-346} }
 @article{chatterji_simon_andres_mizuno_lundsmith_chau_giroux_mah_van landeghem_wu_et al._2018, title={Su1056 - Unraveling Post-Transcriptional Regulation of Intestinal Response to Acute Challenge by the RNA Binding Protein IMP1}, volume={154}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(18)31812-2}, DOI={10.1016/S0016-5085(18)31812-2}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Chatterji, Priya and Simon, Lauren and Andres, Sarah F. and Mizuno, Rei and Lundsmith, Emma and Chau, Lillian and Giroux, Veronique and Mah, Amanda and Van Landeghem, Laurianne and Wu, Gary D. and et al.}, year={2018}, month={May}, pages={S-470} }
 @article{moorefield_andres_blue_van landeghem_mah_santoro_ding_2017, title={Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells}, volume={9}, ISSN={["1945-4589"]}, DOI={10.18632/aging.101279}, abstractNote={Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFPLow), activatable reserve IESC and enteroendocrine cells (Sox9-EGFPHigh), Sox9-EGFPSublow progenitors, and Sox9-EGFPNegative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFPLow IESC and Sox9-EGFPHigh cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging.}, number={8}, journal={AGING-US}, author={Moorefield, Emily C. and Andres, Sarah F. and Blue, R. Eric and Van Landeghem, Laurianne and Mah, Amanda T. and Santoro, M. Agostina and Ding, Shengli}, year={2017}, month={Aug}, pages={1898–1915} }
 @article{coquenlorge_van landeghem_jaulin_cenac_vergnolle_duchalais_neunlist_rolli-derkinderen_2016, title={The arachidonic acid metabolite 11β-ProstaglandinF2α controls intestinal epithelial healing: deficiency in patients with Crohn’s disease}, volume={6}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/SREP25203}, DOI={10.1038/SREP25203}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Coquenlorge, Sabrina and Van Landeghem, Laurianne and Jaulin, Julie and Cenac, Nicolas and Vergnolle, Nathalie and Duchalais, Emilie and Neunlist, Michel and Rolli-Derkinderen, Malvyne}, year={2016}, month={May} }
 @article{hamilton_chatterji_andres_whelan_lundsmith_mizuno_giroux_mah_chau_hicks_et al._2016, title={Tu1850 Direct Regulation of Crypt Autophagy and Intestinal Homeostasis via mRNA Binding Protein Imp1}, volume={150}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(16)33244-9}, DOI={10.1016/S0016-5085(16)33244-9}, abstractNote={tissues.In the gastrointestinal tract, a large amount of studies showed that c-kitis expressed in cells of Cajal, playing an important role in development and function of ICC.But whether or not c-kit is present in another cell type of intestine tract and what roles play in it are still a matter of debate.In the present study, we aimed to investigate the expression, location and function of c-kit in the intestinal epithelium.We demonstrated that c-kit receptor was located and expressed in the proliferative crypt compartment of the colon and small intestine in the normal mice by immunofluorescence, western blotting, and RT-PCR.Furthermore, using the septic KIT mutant mice model, we compared the proliferation and migration of intestinal epithelial cell in vivo BrdU incorporation between the models and normal mice.The results showed that no matter in number of proliferating cell or the distance of migration it is lower in the mutant mice than that in the normal mice.Moreover, the intestinal permeability was decreased in mutant mice model than that in normal mice under the control and endotoxemia condition assessed by with fluorescein-isothiocyanate dextran 4000 in Ussing Chamber.Take together, the c-kit signaling in the intestinal epithelial cell negatively modulated intestinal barrier under control or endotoxemia condition through increased epithelial proliferation and migration resulting in limiting the maturation and differentiation of intestinal epithelial cell.}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Hamilton, Kathryn and Chatterji, Priya and Andres, Sarah and Whelan, Kelly and Lundsmith, Emma and Mizuno, Rei and Giroux, Veronique and Mah, Amanda and Chau, Lillian and Hicks, Philip D. and et al.}, year={2016}, month={Apr}, pages={S960} }
 @article{neunlist_rolli-derkinderen_latorre_van landeghem_coron_derkinderen_de giorgio_2014, title={Enteric Glial Cells: Recent Developments and Future Directions}, volume={147}, ISSN={0016-5085}, url={http://dx.doi.org/10.1053/J.GASTRO.2014.09.040}, DOI={10.1053/J.GASTRO.2014.09.040}, abstractNote={Since their discovery at the end of the 19th century, enteric glial cells (EGCs), the major cellular component of the enteric nervous system, have long been considered mere supportive cells for neurons. However, recent evidence has challenged this view and highlighted their central role in the regulation of gut homeostasis as well as their implication in digestive and extradigestive diseases. In this review, we summarize emerging concepts as to how EGCs regulate neuromediator expression, exert neuroprotective roles, and even act as neuronal as well as glial progenitors in the enteric nervous system. A particularly crucial property of EGCs is their ability to maintain the integrity of the intestinal epithelial barrier, a role that may have important clinical implications not only for digestive diseases, such as postoperative ileus and inflammatory bowel diseases, but also for extradigestive diseases, such as Parkinson disease or obesity. EGCs could also contribute directly to disease processes (eg, inflammation) by their ability to secrete chemokines/cytokines in response to bacterial or inflammatory challenges. Defining the pleiotropic roles exerted by EGCs may reveal better knowledge and help develop new targeted therapeutic options for a variety of gastrointestinal diseases.}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Neunlist, Michel and Rolli-Derkinderen, Malvyne and Latorre, Rocco and Van Landeghem, Laurianne and Coron, Emmanuel and Derkinderen, Pascal and De Giorgio, Roberto}, year={2014}, month={Dec}, pages={1230–1237} }
 @article{guilluy_osborne_van landeghem_sharek_superfine_garcia-mata_burridge_2014, title={Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus}, volume={16}, ISSN={1465-7392 1476-4679}, url={http://dx.doi.org/10.1038/NCB2927}, DOI={10.1038/NCB2927}, abstractNote={Mechanical forces influence many aspects of cell behaviour. Forces are detected and transduced into biochemical signals by force-bearing molecular elements located at the cell surface, in adhesion complexes or in cytoskeletal structures. The nucleus is physically connected to the cell surface through the cytoskeleton and the linker of nucleoskeleton and cytoskeleton (LINC) complex, allowing rapid mechanical stress transmission from adhesions to the nucleus. Although it has been demonstrated that nuclei experience force, the direct effect of force on the nucleus is not known. Here we show that isolated nuclei are able to respond to force by adjusting their stiffness to resist the applied tension. Using magnetic tweezers, we found that applying force on nesprin-1 triggers nuclear stiffening that does not involve chromatin or nuclear actin, but requires an intact nuclear lamina and emerin, a protein of the inner nuclear membrane. Emerin becomes tyrosine phosphorylated in response to force and mediates the nuclear mechanical response to tension. Our results demonstrate that mechanotransduction is not restricted to cell surface receptors and adhesions but can occur in the nucleus.}, number={4}, journal={Nature Cell Biology}, publisher={Springer Science and Business Media LLC}, author={Guilluy, Christophe and Osborne, Lukas D. and Van Landeghem, Laurianne and Sharek, Lisa and Superfine, Richard and Garcia-Mata, Rafael and Burridge, Keith}, year={2014}, month={Mar}, pages={376–381} }
 @article{stevenson_hawkins_sundaram_lund_van landeghem_helmrath_2012, title={Ileocecal resection (ICR)-driven crypt fission requires intestinal epithelial IGF-1 receptor, is increased with delayed IGF-1 therapy, and results in sustained adaptive increases in body weight and intestinal length}, volume={215}, ISSN={1072-7515}, url={http://dx.doi.org/10.1016/j.jamcollsurg.2012.06.212}, DOI={10.1016/j.jamcollsurg.2012.06.212}, abstractNote={Stevenson, Megan A. MD; Hawkins, Jennifer A. MS; Sundaram, Nambirajan PhD; Lund, Kay P. PhD; Van Landeghem, Laurianne PhD; Helmrath, Michael A. MD, FACS Author Information}, number={3}, journal={Journal of the American College of Surgeons}, publisher={Elsevier BV}, author={Stevenson, Megan A. and Hawkins, Jennifer A. and Sundaram, Nambirajan and Lund, P. Kay and Van Landeghem, Laurianne and Helmrath, Michael A.}, year={2012}, month={Sep}, pages={S77} }
 @article{neunlist_van landeghem_mahé_derkinderen_des varannes_rolli-derkinderen_2012, title={The digestive neuronal–glial–epithelial unit: a new actor in gut health and disease}, volume={10}, ISSN={1759-5045 1759-5053}, url={http://dx.doi.org/10.1038/nrgastro.2012.221}, DOI={10.1038/nrgastro.2012.221}, abstractNote={The monolayer of columnar epithelial cells lining the gastrointestinal tract--the intestinal epithelial barrier (IEB)--is the largest exchange surface between the body and the external environment. The permeability of the IEB has a central role in the regulation of fluid and nutrient intake as well as in the control of the passage of pathogens. The functions of the IEB are highly regulated by luminal as well as internal components, such as bacteria or immune cells, respectively. Evidence indicates that two cell types of the enteric nervous system (ENS), namely enteric neurons and enteric glial cells, are potent modulators of IEB functions, giving rise to the novel concept of a digestive 'neuronal-glial-epithelial unit' akin to the neuronal-glial-endothelial unit in the brain. In this Review, we summarize findings demonstrating that the ENS is a key regulator of IEB function and is actively involved in pathologies associated with altered barrier function.}, number={2}, journal={Nature Reviews Gastroenterology & Hepatology}, publisher={Springer Science and Business Media LLC}, author={Neunlist, Michel and Van Landeghem, Laurianne and Mahé, Maxime M. and Derkinderen, Pascal and des Varannes, Stanislas Bruley and Rolli-Derkinderen, Malvyne}, year={2012}, month={Nov}, pages={90–100} }
 @article{bortvedt_santoro_mah_simmons_van landeghem_lund_2011, title={Increased Expression of Insulin Receptor Isoform a (IR-a) and Insulin Receptor Substrate 1 (IRS1) in Poorly Differentiated Colon Cancer Cell Lines and APC MIN/+ Tumors}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)63403-3}, DOI={10.1016/S0016-5085(11)63403-3}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Bortvedt, Sarah and Santoro, Maria A. and Mah, Amanda T. and Simmons, Jim and Van Landeghem, Laurianne and Lund, Pauline K.}, year={2011}, month={May}, pages={S-822} }
 @article{van landeghem_santoro_krebs_mah_dehmer_gracz_magness_lund_2011, title={Insulin-Like Growth Factor-I Promotes Intestinal Stem Cell Expansion During Crypt Regeneration and Mucosal Healing Following Radiation}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)60155-8}, DOI={10.1016/S0016-5085(11)60155-8}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Van Landeghem, Laurianne and Santoro, Maria A. and Krebs, Adrienne E. and Mah, Amanda T. and Dehmer, Jeffrey J. and Gracz, Adam D. and Magness, Scott T. and Lund, Pauline K.}, year={2011}, month={May}, pages={S-39} }
 @article{dehmer_speck_van landeghem_hawkins_lund_helmrath_2011, title={Serum amyloid factor A3: A putative marker of intestinal stem cell expansion}, volume={213}, ISSN={1072-7515}, url={http://dx.doi.org/10.1016/j.jamcollsurg.2011.06.183}, DOI={10.1016/j.jamcollsurg.2011.06.183}, abstractNote={Dehmer, Jeffrey J. MD; Speck, Karen E. MD; Van Landeghem, Laurianne PhD; Hawkins, Jennifer; Lund, Kay P. PhD; Helmrath, Michael A. MD, FACS Author Information}, number={3}, journal={Journal of the American College of Surgeons}, publisher={Elsevier BV}, author={Dehmer, Jeffrey J. and Speck, Karen E. and Van Landeghem, Laurianne and Hawkins, Jennifer and Lund, P. Kay and Helmrath, Michael A.}, year={2011}, month={Sep}, pages={S78} }
 @article{do_landeghem_wielgosz-collin_takoudju_huvelin_kornprobst_bard_barnathan_nazih_2010, title={MS516 Unusual Sterolic Mixture, and 24-isopropylcholesterol, from the sponge Ciocalypta sp. reduce cholesterol uptake and basolateral secretion in Caco2 cells}, volume={11}, ISSN={1567-5688}, url={http://dx.doi.org/10.1016/S1567-5688(10)71016-3}, DOI={10.1016/S1567-5688(10)71016-3}, number={2}, journal={Atherosclerosis Supplements}, publisher={Elsevier BV}, author={Do, Q. and Landeghem, L. and Wielgosz-Collin, G. and Takoudju, M. and Huvelin, J.-M. and Kornprobst, J.-M. and Bard, J.-M. and Barnathan, G. and Nazih, H.}, year={2010}, month={Jun}, pages={213} }
 @article{do_van landeghem_wielgosz-collin_takoudju_huvelin_kornprobst_bard_barnathan_nazih_2009, title={Unusual sterolic mixture, and 24-isopropylcholesterol, from the spongeCiocalyptasp. reduce cholesterol uptake and basolateral secretion in Caco-2 cells}, volume={106}, ISSN={0730-2312 1097-4644}, url={http://dx.doi.org/10.1002/jcb.22047}, DOI={10.1002/jcb.22047}, abstractNote={Abstract}, number={4}, journal={Journal of Cellular Biochemistry}, publisher={Wiley}, author={Do, Hong Quang and Van Landeghem, Laurianne and Wielgosz-Collin, Gaëtane and Takoudju, Martin and Huvelin, Jean-Michel and Kornprobst, Jean-Michel and Bard, Jean-Marie and Barnathan, Gilles and Nazih, Hassan}, year={2009}, month={Mar}, pages={659–665} }
 @article{van landeghem_derkinderen_aubert_enslen_guisle-marsollier_léger_galmiche_savidge_neunlist_2008, title={T1820 Enteric Glial Cells Promote Wound Healing of Intestinal Epithelial Barrier in Part Via a FAK-Dependent Pathway}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(08)62661-X}, DOI={10.1016/S0016-5085(08)62661-X}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Van Landeghem, Laurianne and Derkinderen, Pascal and Aubert, Philippe and Enslen, Hervé and Guisle-Marsollier, Isabelle and Léger, Jean and Galmiche, Jean Paul and Savidge, Tor and Neunlist, Michel}, year={2008}, month={Apr}, pages={A-570} }