Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition (PAIso-Seq)

ABSTRACT: The transition of mammalian early epiblast at different phases is characterized by the differences of pluripotent states and developmental potential, involving extensive transcriptome changes. However, the role of post-transcriptional RNA degradation modulation in cell fate transition remains largely unexplored. Here, we report that deadenylase Cnot8 of Ccr4-Not complex specifically plays a role in naïve-to-formative transition of pluripotent stem cells (PSCs). Disruption of Cnot8 results in early embryonic lethality, accompanying with the increased expression levels of naïve transcription factors in mouse epiblasts. Cnot8 depletion leads to accumulated expression abundances and increased poly(A) tail lengths of massive transcripts including mRNAs of naïve regulation networks, impairing the naïve-to-formative pluripotency conversion. Mechanistically, Cnot8 interacts with Tob1 and Pabpc1 to guarantee the prompt mRNA deadenylation and degradation of naïve regulation networks at specific time. Together, these findings delineate the mechanism underlying PSC fate transition through global degradation of mRNAs for naïve regulation networks by Cnot8.

ORGANISM(S): Mus musculus

PROVIDER: GSE174423 | GEO | 2022/05/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition (RNA-Seq)

Project description:The transition of mammalian early epiblast at different phases is characterized by the differences of pluripotent states and developmental potential, involving extensive transcriptome changes. However, the role of post-transcriptional RNA degradation modulation in cell fate transition remains largely unexplored. Here, we report that deadenylase Cnot8 of Ccr4-Not complex specifically plays a role in naïve-to-formative transition of pluripotent stem cells (PSCs). Disruption of Cnot8 results in early embryonic lethality, accompanying with the increased expression levels of naïve transcription factors in mouse epiblasts. Cnot8 depletion leads to accumulated expression abundances and increased poly(A) tail lengths of massive transcripts including mRNAs of naïve regulation networks, impairing the naïve-to-formative pluripotency conversion. Mechanistically, Cnot8 interacts with Tob1 and Pabpc1 to guarantee the prompt mRNA deadenylation and degradation of naïve regulation networks at specific time. Together, these findings delineate the mechanism underlying PSC fate transition through global degradation of mRNAs for naïve regulation networks by Cnot8.

2022-05-11 | GSE174424 | GEO

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition [scRNA-Seq]

2022-05-11 | GSE194431 | GEO

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotent Transition

Project description:Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotent Transition

| PRJNA729787 | ENA

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition [scRNA-Seq]

Project description:Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition [scRNA-Seq]

| PRJNA800646 | ENA

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition (PAIso-Seq)

Project description:Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition (PAIso-Seq)

| PRJNA729864 | ENA

Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition (RNA-Seq)

Project description:Cnot8 Eliminates Naïve Regulation Networks and Is Essential for Naïve-to-Formative Pluripotency Transition (RNA-Seq)

| PRJNA729863 | ENA

Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency

Project description:In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre- to post-implantation epiblast in utero. We identified 496 naïve state-associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition.

2020-12-22 | GSE145653 | GEO

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