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Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2, Glis1, Essrb and Sall4 [scRNA-seq]

ABSTRACT: Reprogramming somatic cells to pluripotency has revolutionized our understanding of cell fate control. Yet, most of that knowledge has been predicated on a single system powered by Oct4, Sox2, Klf4 and Myc. Here we describe two four factor sets capable of reprogramming mouse embryonic fibroblasts (MEFs) to pluripoten-cy. We first developed Jdp2, Glis1, Essrb and Sall4 or JGES that can mediate ro-bust reprogramming by orchestrating a unique chromatin accessibility dynamics involving loci encoding genes for mitochondrial respiration and meiosis/germ cell development. Single cell sequencing further reveals early Sox2+ intermediates as well as late neuron-, hematoendothelial-, mesoderm-, visceral endoderm- and plu-ripotent-like fates. Along a fate continuum, we show distinct transitions of differen-tially expressed genes marked by a critical crossover point. Among genes sus-tained after the point, we identify Zfp296, Etv5, Sall1 and Tfap2c or ZEST that can reprogram MEFs to pluripotency. Our study suggests that the JGES and ZEST sys-tem may allow deeper understanding of cell fate control.

ORGANISM(S): Mus musculus

PROVIDER: GSE145388 | GEO | 2022/11/05

REPOSITORIES: GEO

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