@article{clark_buckner_fisher_nelson_nguyen_simmons_balaguer_butler-smith_sheldon_bergmann_et al._2019, title={Stem-cell-ubiquitous genes spatiotemporally coordinate division through regulation of stem-cell-specific gene networks}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-13132-2}, abstractNote={AbstractStem cells are responsible for generating all of the differentiated cells, tissues, and organs in a multicellular organism and, thus, play a crucial role in cell renewal, regeneration, and organization. A number of stem cell type-specific genes have a known role in stem cell maintenance, identity, and/or division. Yet, how genes expressed across different stem cell types, referred to here as stem-cell-ubiquitous genes, contribute to stem cell regulation is less understood. Here, we find that, in the Arabidopsis root, a stem-cell-ubiquitous gene, TESMIN-LIKE CXC2 (TCX2), controls stem cell division by regulating stem cell-type specific networks. Development of a mathematical model of TCX2 expression allows us to show that TCX2 orchestrates the coordinated division of different stem cell types. Our results highlight that genes expressed across different stem cell types ensure cross-communication among cells, allowing them to divide and develop harmonically together.}, journal={NATURE COMMUNICATIONS}, author={Clark, Natalie M. and Buckner, Eli and Fisher, Adam P. and Nelson, Emily C. and Nguyen, Thomas T. and Simmons, Abigail R. and Balaguer, Maria A. de Luis and Butler-Smith, Tiara and Sheldon, Parnell J. and Bergmann, Dominique C. and et al.}, year={2019}, month={Dec} } @article{spurney_broeck_clark_fisher_balaguer_sozzani_2020, title={tuxnet: a simple interface to process RNA sequencing data and infer gene regulatory networks}, volume={101}, ISSN={["1365-313X"]}, url={https://doi.org/10.1111/tpj.14558}, DOI={10.1111/tpj.14558}, abstractNote={SummaryPredicting gene regulatory networks (GRNs) from expression profiles is a common approach for identifying important biological regulators. Despite the increased use of inference methods, existing computational approaches often do not integrate RNA‐sequencing data analysis, are not automated or are restricted to users with bioinformatics backgrounds. To address these limitations, we developed tuxnet, a user‐friendly platform that can process raw RNA‐sequencing data from any organism with an existing reference genome using a modified tuxedo pipeline (hisat 2 + cufflinks package) and infer GRNs from these processed data. tuxnet is implemented as a graphical user interface and can mine gene regulations, either by applying a dynamic Bayesian network (DBN) inference algorithm, genist, or a regression tree‐based pipeline, rtp‐star. We obtained time‐course expression data of a PERIANTHIA (PAN) inducible line and inferred a GRN using genist to illustrate the use of tuxnet while gaining insight into the regulations downstream of the Arabidopsis root stem cell regulator PAN. Using rtp‐star, we inferred the network of ATHB13, a downstream gene of PAN, for which we obtained wild‐type and mutant expression profiles. Additionally, we generated two networks using temporal data from developmental leaf data and spatial data from root cell‐type data to highlight the use of tuxnet to form new testable hypotheses from previously explored data. Our case studies feature the versatility of tuxnet when using different types of gene expression data to infer networks and its accessibility as a pipeline for non‐bioinformaticians to analyze transcriptome data, predict causal regulations, assess network topology and identify key regulators.}, number={3}, journal={PLANT JOURNAL}, author={Spurney, Ryan J. and Broeck, Lisa and Clark, Natalie M. and Fisher, Adam P. and Balaguer, Maria A. de Luis and Sozzani, Rosangela}, year={2020}, month={Feb}, pages={716–730} } @article{balaguer_fisher_clark_fernandez-espinosa_moller_weijers_lohmann_williams_lorenzo_sozzani_et al._2017, title={Predicting gene regulatory networks by combining spatial and temporal gene expression data in Arabidopsis root stem cells}, volume={114}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1707566114}, abstractNote={Significance We developed a computational pipeline that uses gene expression datasets for inferring relationships among genes and predicting their importance. We showed that the capacity of our pipeline to integrate spatial and temporal transcriptional datasets improves the performance of inference algorithms. The combination of this pipeline with Arabidopsis stem cell-specific data resulted in networks that capture the regulations of stem cell-enriched genes in the stem cells and throughout root development. Our combined approach of molecular biology, computational biology, and mathematical biology, led to successful findings of factors that could play important roles in stem cell regulation and, in particular, quiescent center function. }, number={36}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Balaguer, M. A. D. and Fisher, A. P. and Clark, N. M. and Fernandez-Espinosa, M. G. and Moller, B. K. and Weijers, D. and Lohmann, J. U. and Williams, C. and Lorenzo, O. and Sozzani, Rosangela and et al.}, year={2017}, month={Sep}, pages={E7632–E7640} } @article{fisher_sozzani_2016, title={Gene and networks regulating the root stem cell niche of Arabidopsis}, volume={29}, ISSN={["1879-0356"]}, DOI={10.1016/j.pbi.2015.11.002}, abstractNote={Stem cells are the source of different cell types and tissues in all multicellular organisms. In plants, the balance between stem cell self-renewal and differentiation of their progeny is crucial for correct tissue and organ formation. How transcriptional programs precisely control stem cell maintenance and identity, and what are the regulatory programs influencing stem cell asymmetric cell division (ACD), are key questions that researchers have sought to address for the past decade. Successful efforts in genetic, molecular, and developmental biology, along with mathematical modeling, have identified some of the players involved in stem cell regulation. In this review, we will discuss several studies that characterized many of the genetic programs and molecular mechanisms regulating stem cell ACD and their identity in the Arabidopsis root. We will also highlight how the growing use of mathematical modeling provides a comprehensive and quantitative perspective on the design rules governing stem cell ACDs.}, journal={Curr Opin Plant Biol}, author={Fisher, A.P. and Sozzani, R.}, year={2016}, month={Feb}, pages={38–43} } @article{clark_hinde_winter_fisher_crosti_blilou_gratton_benfey_sozzani_2016, title={Tracking transcription factor mobility and interaction in Arabidopsis roots with fluorescence correlation spectroscopy}, volume={5}, journal={Elife}, author={Clark, N. M. and Hinde, E. and Winter, C. M. and Fisher, A. P. and Crosti, G. and Blilou, I. and Gratton, E. and Benfey, P. N. and Sozzani, R.}, year={2016} } @misc{kajala_ramakrishna_fisher_bergmann_de smet_sozzani_weijers_brady_2014, title={Omics and modelling approaches for understanding regulation of asymmetric cell divisions in arabidopsis and other angiosperm plants}, volume={113}, ISSN={["1095-8290"]}, DOI={10.1093/aob/mcu065}, abstractNote={BACKGROUND Asymmetric cell divisions are formative divisions that generate daughter cells of distinct identity. These divisions are coordinated by either extrinsic ('niche-controlled') or intrinsic regulatory mechanisms and are fundamentally important in plant development. SCOPE This review describes how asymmetric cell divisions are regulated during development and in different cell types in both the root and the shoot of plants. It further highlights ways in which omics and modelling approaches have been used to elucidate these regulatory mechanisms. For example, the regulation of embryonic asymmetric divisions is described, including the first divisions of the zygote, formative vascular divisions and divisions that give rise to the root stem cell niche. Asymmetric divisions of the root cortex endodermis initial, pericycle cells that give rise to the lateral root primordium, procambium, cambium and stomatal cells are also discussed. Finally, a perspective is provided regarding the role of other hormones or regulatory molecules in asymmetric divisions, the presence of segregated determinants and the usefulness of modelling approaches in understanding network dynamics within these very special cells. CONCLUSIONS Asymmetric cell divisions define plant development. High-throughput genomic and modelling approaches can elucidate their regulation, which in turn could enable the engineering of plant traits such as stomatal density, lateral root development and wood formation.}, number={7}, journal={ANNALS OF BOTANY}, author={Kajala, Kaisa and Ramakrishna, Priya and Fisher, Adam and Bergmann, Dominique C. and De Smet, Ive and Sozzani, Rosangela and Weijers, Dolf and Brady, Siobhan M.}, year={2014}, month={Jun}, pages={1083–1105} }