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

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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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Induction of Pluripotency by Alternative Factors (RNA-Seq)

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2019-06-18 | GSE127927 | GEO

Induction of Pluripotency by Alternative Factors (ATAC-Seq)

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 seven factor combination, Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F), that reprogram MEFs to chimera competent iPSCs efficiently. RNA- and ATAC-seq reveal differences between 7F and Yamanaka induced pluripotency, 7IP and YIP, 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.

2019-06-18 | GSE127926 | GEO

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Localization of the Rb tumor suppressor in MEFs during reprogramming to iPS and the consequence of Rb loss on the transcriptional profile and histone landscape in these cells

Project description:The reprogramming of differentiated cells to an embryonic stem cell-like state provides a powerful system to explore fundamental mechanisms of development, including how mammalian cells establish and maintain pluripotency and long-term self-renewal capability. Based on the similarities between embryonic stem cells and cancer cells, we investigated the potential role of the retinoblastoma tumor suppressor and cell cycle regulator RB in the reprogramming of fibroblasts into induced pluripotent stem cells (iPS cells). Herein we demonstrate that loss of RB function leads to both an acceleration of the reprogramming process and the generation of more iPS clones from fibroblasts. This effect is largely due to a restrictive role for RB at the early stages of reprogramming. Surprisingly, however, RB inactivation does not enhance the formation of iPS clones by accelerating the proliferation of cells undergoing reprogramming. Rather, a genome-wide investigation of RB targets indicates that RB binds to regulatory regions of pluripotency genes such as Sox2 and Oct4 and contributes to their full repression in differentiated cells. This effect correlates with the maintenance of a repressive chromatin structure at these loci. Accordingly, Rb-deficient fibroblasts can be reprogrammed into iPS cells even in the absence of exogenous Sox2, which is normally required to initiate reprogramming from fibroblasts. These experiments identify a novel barrier in the reprogramming process, mainly the repression of certain pluripotency genes such as Sox2 by RB, which provides a new link between tumor suppressor mechanisms and cellular reprogramming. RNAseq from MEFs with 2 biological replicates (save CP), Rb ChIPseq from MEFs with 2 biological replicates, Histone H3 modification ChIPseq from MEFs with 1 biological replicate

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Extensive protein group SUMO modification of repressive chromatin factors distinguishes pluripotent from somatic cells

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2020-09-16 | PXD017697 | Pride

Extensive protein group SUMO modification of repressive chromatin factors distinguishes pluripotent from somatic cells (total proteome)

2020-09-16 | PXD020287 | Pride

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