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Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2, Glis1, Essrb and Sall4

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE140008 | GEO | 2022/11/05

REPOSITORIES: GEO

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Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2, Glis1, Essrb and Sall4 (dataset II)

Project description:Reprogramming somatic cells to pluripotency represents a paradigm for cell fate determination. A binary logic of closing and opening chromatin provides a simple way to understand iPSC reprogramming driven by both Yamanaka factors or chemicals. Here we apply this logic to the design a four factor combination, Jdp2, Glis1, Essrb and Sall4 (4F), that reprogram MEFs to chimera competent iPSCs efficiently. RNA- and ATAC-seq reveal differences between JGES and 7F induced pluripotency, 7IP and JGES IP, in transcriptomic and chromatin accessibility dynamics(CAD). Sall4 emerges as a dominant force that can close and open chromatin with the help of Jdp2 and Glis1 in resetting somatic chromatin to a pluripotent state. These results reveal a previously unknown path between somatic and pluripotent states, open a door for cell fate control.

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

Project description: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.

2022-11-05 | GSE145388 | GEO