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Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells

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

ORGANISM(S): Mus musculus

PROVIDER: GSE85029 | GEO | 2017/03/16

SECONDARY ACCESSION(S): PRJNA335995

REPOSITORIES: GEO

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DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.

Project description:Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. We show that embryonic stem cells (ESCs) mainly express DIDO3 and that their differentiation after leukemia inhibitory factor withdrawal requires DIDO1 expression. C-terminal truncation of DIDO3 (Dido3?CT) impedes ESC differentiation while retaining self-renewal; small hairpin RNA-Dido1 ESCs have the same phenotype. Dido3?CT ESC differentiation is rescued by ectopic expression of DIDO3, which binds the Dido locus via H3K4me3 and RNA POL II and induces DIDO1 expression. DIDO1, which is exported to cytoplasm, associates with, and is N-terminally phosphorylated by PKCiota. It binds the E3 ubiquitin ligase WWP2, which contributes to cell fate by OCT4 degradation, to allow expression of primitive endoderm (PE) markers. PE formation also depends on phosphorylated DIDO3 localization to centrosomes, which ensures their correct positioning for PE cell polarization. We propose that DIDO isoforms act as a switchboard that regulates genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation.

| S-EPMC5390109 | biostudies-other

Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (vsmutCT)

Project description:Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. Embryonic stem cells (ESC) strongly express Dido3, whose C-terminal truncation impedes ESC differentiation while retaining self-renewal. We show that Dido3 binds to its gene locus via H3K4me3 and RNA pol II and, at differentiation onset, induces expression of its splice variant Dido1, which then leads to Dido3 degradation and downregulation of stemness genes. We propose that Dido isoforms act as a switchboard to regulate genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation. We used microarrays to determine how the deletion of exon 16 (C-terminal truncation) of the Dido3 affects gene expression that results in the suppression of ESC differentiation.

2017-03-16 | GSE85026 | GEO

Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (Affy)

2017-03-16 | GSE85006 | GEO

Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (vsmutNT)

2017-03-16 | GSE85027 | GEO

Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (vsmut)

2017-03-16 | GSE85025 | GEO

Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (ChIP-seq)

2017-03-16 | GSE85028 | GEO

Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells

Project description:Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells

| PRJNA335995 | ENA

Bach1 regulates self-renewal and impedes mesendodermal differentiation of human embryonic stem cells.

Project description:The transcription factor BTB and CNC homology 1 (Bach1) is expressed in the embryos of mice, but whether Bach1 regulates the self-renewal and early differentiation of human embryonic stem cells (hESCs) is unknown. We report that the deubiquitinase ubiquitin-specific processing protease 7 (Usp7) is a direct target of Bach1, that Bach1 interacts with Nanog, Sox2, and Oct4, and that Bach1 facilitates their deubiquitination and stabilization via the recruitment of Usp7, thereby maintaining stem cell identity and self-renewal. Bach1 also interacts with polycomb repressive complex 2 (PRC2) and represses mesendodermal gene expression by recruiting PRC2 to the genes' promoters. The loss of Bach1 in hESCs promotes differentiation toward the mesendodermal germ layers by reducing the occupancy of EZH2 and H3K27me3 in mesendodermal gene promoters and by activating the Wnt/?-catenin and Nodal/Smad2/3 signaling pathways. Our study shows that Bach1 is a key determinant of pluripotency, self-renewal, and lineage specification in hESCs.

| S-EPMC6415956 | biostudies-literature

Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells.

Project description:Embryonic stem cells (ESCs) are pluripotent stem cells from early embryos. It has been well recognized that ESC genomes are maintained in a globally transcriptional hyperactive state, which genetically poised ESCs to the high differentiation potential. However, the transcription factors regulating the global transcription activities in ESCs are not well defined. We show here that mouse and human ESCs express two transcription factors, Aire and Deaf1. Previously known to function in the thymus stromal cells and peripheral lymphoid organs respectively, Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance. Differentiation of ESCs greatly reduced Aire and Deaf1 expression, in a pattern similar to the pluripotent factors, Oct4 and Nanog. Knockdown of Aire in mouse ESCs resulted in significantly decreased clone-forming efficiency as well as attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. In addition, some differentiation-associated genes that are sporadically expressed in ESCs were reduced in expression upon Aire knockdown. These results suggest that transcription factors such as Aire and Deaf1, which exert global transcriptional regulatory functions, may play important roles in self-renewal of ESCs and maintaining ESC in a transcriptionally hyperactive state.

| S-EPMC2885885 | biostudies-literature

KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-27 | E-GEOD-53093 | biostudies-arrayexpress