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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE140007 | 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 [RNA-seq]

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Project description:We report that Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F) convert MEFs to chimera competent iPSCs with fast kinetics. Time lapse microscopy reveal morphological changes distinct for 7F and Yamanaka factor (YF) reprogramming. Bulk transcriptomic analyses suggest that 7F and YF share 927 up and 548 down regulated genes, but differ in 1138 YF and 427 7F specifically activated genes. Single cell RNA sequencing reveals a fate path that can be further resolved into a cell fate continuum based on a MEF/ESC scoring system. A crossing point marks the transition in the continuum from somatic to pluripotent fates. By sampling the leading cells along this continuum, we identified transition stages marked by novel nu-clear factors and cell surface molecules. Our results reveal an efficient path to pluripotency and suggest that cell fate is governed by intrinsic fac-tors accessible by diverse approaches

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