2020 journal article

Derivation of stable embryonic stem cell-like, but transcriptionally heterogenous, induced pluripotent stem cells from non-permissive mouse strains

MAMMALIAN GENOME, 31(9-12), 263–286.

By: T. Garbutt n, K. Konganti*, T. Konneker n, A. Hillhouse *, D. Phelps n , A. Jones n, D. Aylor n, D. Threadgill*

MeSH headings : Animals; Biomarkers; Cell Differentiation; Cells, Cultured; Cellular Reprogramming / genetics; Embryonic Stem Cells / cytology; Embryonic Stem Cells / metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genetic Heterogeneity; Immunophenotyping; Induced Pluripotent Stem Cells / cytology; Induced Pluripotent Stem Cells / metabolism; Mice; Platelet Endothelial Cell Adhesion Molecule-1; Species Specificity; Transcriptome
TL;DR: Heterogeneity is a naturally occurring, necessary quality of stem cells that allows for the maintenance of pluripotency and this study is the first study to derive stable ESC-like stem cells from the non-permissive NOD/ShiLtJ and WSB/EiJ strains, enabling easier and broader research possibilities into pluripOTency for these and similar non-Permissive mouse strains and species. (via Semantic Scholar)
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Source: Web Of Science
Added: October 19, 2020

Genetic background is known to play a role in the ability to derive pluripotent, embryonic stem cells (ESC), a trait referred to as permissiveness. Previously we demonstrated that induced pluripotent stem cells (iPSC) can be readily derived from non-permissive mouse strains by addition of serum-based media supplemented with GSK3B and MEK inhibitors, termed 2iS media, 3 days into reprogramming. Here, we describe the derivation of second type of iPSC colony from non-permissive mouse strains that can be stably maintained independently of 2iS media. The resulting cells display transcriptional heterogeneity similar to that observed in ESC from permissive genetic backgrounds derived in conventional serum containing media supplemented with leukemia inhibitor factor. However, unlike previous studies that report exclusive subpopulations, we observe both exclusive and simultaneous expression of naive and primed cell surface markers. Herein, we explore shifts in pluripotency in the presence of 2iS and characterize heterogenous subpopulations to determine their pluripotent state and role in heterogenous iPSCs derived from the non-permissive NOD/ShiLtJ strain. We conclude that heterogeneity is a naturally occurring, necessary quality of stem cells that allows for the maintenance of pluripotency. This study further demonstrates the efficacy of the 2iS reprogramming technique. It is also the first study to derive stable ESC-like stem cells from the non-permissive NOD/ShiLtJ and WSB/EiJ strains, enabling easier and broader research possibilities into pluripotency for these and similar non-permissive mouse strains and species.