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FoxO transcription factors actuate the formative pluripotency specific gene expression programme

ABSTRACT: FoxO transcription factors actuate the formative pluripotency specific gene expression programme

PROVIDER: PRJNA1065862 | ENA |

REPOSITORIES: ENA

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FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ChIP-Seq]

Project description:Naïve pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naïve pluripotency-specific transcription factors (TFs). Upon exiting naïve pluripotency, ES cells transition through a formative post-implantation-like pluripotent state. However, the mechanisms underlying disengagement from the naïve GRN and initiation of the formative GRN remain unclear. Here, we demonstrate that phosphorylated AKT acts as a gatekeeper that prevents nuclear localization of FoxO TFs in naïve ESCs. PTEN-mediated reduction of AKT activity allows nuclear entry by FoxO TFs, enforcing a cell fate transition by binding and activating formative pluripotency-specific enhancers. Indeed, FoxO TFs are necessary and sufficient for transition from the naïve to the formative pluripotent state. Our work uncovers a pivotal role for FoxO TFs and AKT signalling in mechanisms underlying the exit from naïve pluripotency, a critical early embryonic cell fate transition.

2024-07-25 | GSE253479 | GEO

FoxO transcription factors actuate the formative pluripotency specific gene expression programme [RNA-Seq]

2024-07-25 | GSE253473 | GEO

FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ATAC-Seq]

2024-07-25 | GSE253472 | GEO

FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ChIP-Seq]

Project description:FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ChIP-Seq]

| PRJNA1065872 | ENA

FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ATAC-Seq]

Project description:FoxO transcription factors actuate the formative pluripotency specific gene expression programme [ATAC-Seq]

| PRJNA1065871 | ENA

FoxO transcription factors actuate the formative pluripotency specific gene expression programme [RNA-Seq]

Project description:FoxO transcription factors actuate the formative pluripotency specific gene expression programme [RNA-Seq]

| PRJNA1065870 | ENA

FoxO transcription factors actuate the formative pluripotency specific gene expression programme

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-07-25 | GSE253480 | GEO

Three Transcription Factor Functions Empower Formative Transition from Naïve Pluripotency [ChIP-Seq]

Project description:The gene regulatory network in naïve mouse embryonic stem cells (ESC) is reconfigured to enable lineage commitment. Tcf3 sanctions rewiring to formative pluripotency by suppressing components of the ESC transcription factor circuitry. However, Tcf3 depletion only delays, and does not prevent transition. Here we delineate major contributions of Ets-family transcription factor Etv5 and the repressor Rbpj. ERK signalling triggers genome relocation of Etv5 to commission formative pluripotency enhancers. Concomitant up-regulation of Rbpj prevents reversion by repressing potent naïve factors, Nanog and Tbx3. Triple deletion of Etv5, Rbpj and Tcf3 disables naïve ESC, such that they remain undifferentiated and locked in self-renewal even in the presence of differentiation stimuli. Thus, pluripotency dynamics are driven by combined action of two repressors that respectively dissolve and extinguish the naive network, and an activator that initiates transcription of formative network genes. Similar tripartite modality might be a general requirement for robust cell state transitions.

2019-05-09 | GSE122239 | GEO

Three Transcription Factor Functions Empower Progression from Naïve to Formative Pluripotency [RNA-Seq]

Project description:The gene regulatory network in naïve mouse embryonic stem cells (ESCs) must be reconfigured for lineage competence. Tcf3 enables rewiring to formative pluripotency by repressing components of the ESC transcription factor circuitry. However, elimination of Tcf3 only delays, and does not prevent, state transition. Here we delineate distinct contributions of the Ets-family transcription factor Etv5 and the repressor Rbpj. Downstream of Erk1/2 signalling, Etv5 activates enhancers for formative pluripotency. Concomitant up-regulation of Rbpj ensures irreversible exit from the naïve state by extinguishing reversal factors, Nanog and Tbx3. Triple deletion of Etv5, Rbpj and Tcf3 incapacitates ESCs, such that they remain undifferentiated and locked in self-renewal even in the presence of differentiation stimuli. Thus, pluripotency progression is driven hierarchically by two repressors, that respectively dissolve and extinguish the naive network, and an initiator that commissions the formative network. Similar tripartite action may be a general mechanism for efficient cell transitions.

2019-05-09 | GSE121148 | GEO

Formative transition of human naïve pluripotent stem cells

Project description:Human naïve pluripotent stem cells (PSC) share features with pre-implantation epiblast. They thus provide an unmatched opportunity for characterising the developmental programme of pluripotency in Homo sapiens. Here we confirm that naïve PSC do not respond directly to germ layer induction, but must first acquire competence. Capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of Wnt signalling. Whole transcriptome profiling during this formative transition highlights dynamic changes in gene expression, affecting many cellular properties, including metabolism and epithelialisation. Notably, naïve pluripotency factors are exchanged for post-implantation factors, but competent cells remain devoid of lineage primed transcription. The gradual pace of transition for human naïve PSC is consistent with the timespan of primate development from blastocyst to gastrulation. Transcriptome trajectory during in vitro capacitation of human naïve cells tracks the progression of epiblast during embryogenesis in Macaca fascicularis, but shows greater divergence from mouse development. Thus the formative transition of naïve PSC in a simple culture system may recapitulate essential and specific features of pluripotency dynamics during an inaccessible period of human embryogenesis.

2019-03-07 | GSE123055 | GEO

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