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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation

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

ORGANISM(S): Mus musculus

PROVIDER: GSE159430 | GEO | 2022/06/07

REPOSITORIES: GEO

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Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation : In memoriam Professor Niels Borregaard.

Project description:Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of Cdk1/2/4 inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.

| S-EPMC9225994 | biostudies-literature

Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation [ChIP-Seq_2]

2022-06-07 | GSE189621 | GEO

Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [RNA-Seq]

Project description:Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues. However, how this temporal process of cell cycle exit and induction of lineage-specific transcription programs is coordinated remains largely unknown. To understand the underlying mechanisms, we investigated how the tissue-specific transcription factors CEBPA and CEBPE coordinate cell cycle exit and lineage-specification during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-commitment by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of Cdk1/2/4 inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with terminal differentiation through the use of distinct gene regulatory elements.

2022-06-07 | GSE159428 | GEO

Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [ChIP-Seq]

2022-06-07 | GSE159395 | GEO

Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation

Project description:Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation

| PRJNA668912 | ENA

Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation [ChIP-Seq_2]

Project description:Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation [ChIP-Seq_2]

| PRJNA783900 | ENA

Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [RNA-Seq]

Project description:Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [RNA-Seq]

| PRJNA668916 | ENA

Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [ChIP-Seq]

Project description:Transcription factor-driven coordination of cell cycle exit and specification of cell identify during granulocytic differentiation [ChIP-Seq]

| PRJNA668763 | ENA

Dynamics of the 4D genome during in vivo lineage specification and differentiation.

Project description:Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. Our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.

| S-EPMC7264236 | biostudies-literature

Integral bHLH factor regulation of cell cycle exit and RGC differentiation.

Project description:BACKGROUND:In the developing mouse embryo, the bHLH transcription factor Neurog2 is transiently expressed by retinal progenitor cells and required for the initial wave of neurogenesis. Remarkably, another bHLH factor, Ascl1, normally not present in the embryonic Neurog2 retinal lineage, can rescue the temporal phenotypes of Neurog2 mutants. RESULTS:Here we show that Neurog2 simultaneously promotes terminal cell cycle exit and retinal ganglion cell differentiation, using mitotic window labeling and integrating these results with retinal marker quantifications. We also analyzed the transcriptomes of E12.5 GFP-expressing cells from Neurog2GFP/+ , Neurog2GFP/GFP , and Neurog2Ascl1KI/GFP eyes, and validated the most significantly affected genes using qPCR assays. CONCLUSIONS:Our data support the hypothesis that Neurog2 acts at the top of a retinal bHLH transcription factor hierarchy. The combined expression levels of these downstream factors are sufficiently induced by ectopic Ascl1 to restore RGC genesis, highlighting the robustness of this gene network during retinal ganglion cell neurogenesis. Developmental Dynamics 247:965-975, 2018. © 2018 Wiley Periodicals, Inc.

| S-EPMC6105502 | biostudies-literature

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