Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of PRC2 enables self-renewal of naïve pluripotent stem cells from chimpanzee

ABSTRACT: Naïve pluripotent stem cells (nPSCs) correspond to nascent epiblast in the pre-implantation embryo. nPSCs from mouse and human differ in self-renewal requirements and potency for trophectoderm generation. Here we investigated chimpanzee (Pan troglodytes) nPSCs. Naïve type colonies emerged after resetting or reprogramming but failed to expand. We found that the block to self-renewal is overcome by inhibition of EZH2, the enzymatic component of Polycomb repressor group 2 (PRC2). Chimpanzee nPSCs are euploid, produce teratomas, and can be capacitated for somatic lineage differentiation in vitro. They show transcriptome relatedness to human nPSCs and early epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee nPSCs differentiate to trophectoderm and form tri-lineage blastoids. We confirmed that PRC2 suppresses self-renewal by genetic deletions. Furthermore, we demonstrate that EZH2 inhibition facilitates feeder-free propagation of human nPSCs. In summary, chimpanzee nPSCs expand the repertoire of systems for studying primate pluripotency and early embryogenesis.

ORGANISM(S): Pan troglodytes

PROVIDER: GSE278810 | GEO | 2025/02/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inhibition of PRC2 enables self-renewal of naïve pluripotent stem cells from chimpanzee [bisulfite-seq]

Project description:Naïve pluripotent stem cells (nPSCs) correspond to nascent epiblast in the pre-implantation embryo. nPSCs from mouse and human differ in self-renewal requirements and potency for trophectoderm generation. Here we investigated chimpanzee (Pan troglodytes) nPSCs. Naïve type colonies emerged after resetting or reprogramming but failed to expand. We found that the block to self-renewal is overcome by inhibition of EZH2, the enzymatic component of Polycomb repressor group 2 (PRC2). Chimpanzee nPSCs are euploid, produce teratomas, and can be capacitated for somatic lineage differentiation in vitro. They show transcriptome relatedness to human nPSCs and early epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee nPSCs differentiate to trophectoderm and form tri-lineage blastoids. We confirmed that PRC2 suppresses self-renewal by genetic deletions. Furthermore, we demonstrate that EZH2 inhibition facilitates feeder-free propagation of human nPSCs. In summary, chimpanzee nPSCs expand the repertoire of systems for studying primate pluripotency and early embryogenesis.

2025-02-26 | GSE282157 | GEO

Inhibition of PRC2 enables self-renewal of naïve pluripotent stem cells from chimpanzee

2025-02-26 | GSE264735 | GEO

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [RNA-seq]

Project description:The first lineage choice made in human embryo development separates trophectoderm from the inner cell mass, which proceeds to form the pluripotent epiblast and primitive endoderm. Trophectoderm on the other hand gives rise to the placenta. Naïve pluripotent stem cells are derived from the pluripotent epiblast of the blastocyst and offer possibilities to explore how lineage integrity is maintained. Here, we discover that Polycomb repressive complex 2 (PRC2) restricts an intrinsic capacity of naïve pluripotent stem cells to give rise to trophectoderm. Through quantitative epigenome profiling, we find that broad histone H3 lysine 27 trimethylation (H3K27me3) hypermethylation is a common feature of naïve pluripotency across species. We define a previously unappreciated, naïve-specific set of bivalent promoters, featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm transcription factors in a transcriptionally poised state that is resolved to an active state upon depletion of H3K27me3 via inhibition of the enzymatic subunits of PRC2, EZH1/2. Conversely, primed human embryonic stem cells cannot be driven towards trophectoderm development via PRC2 inhibition. While naïve and primed hESCs share the majority of bivalent promoters, PRC2 contributes to the repression of largely non-overlapping subsets of these promoters in each state, hence H3K27me3-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

2021-08-23 | GSE181242 | GEO

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [ChIP-seq]

2021-08-23 | GSE181241 | GEO

Males undergo a transient X-chromosome inactivation-like state at the onset of naïve cell differentiation

Project description:A hallmark of naïve cell identity is the presence of two active X-chromosomes in females. However, little is known if the naïve gene network prevents the initiation of X-chromosome-inactivation (XCI). Here, we demonstrate that robust naïve pluripotent stem cell (nPSC) self-renewal abolishes expression of Xist, the master regulator of XCI. Intriguingly, at the onset of differentiation when nPSCs become Nanog-negative they accumulate Xist on the male X-chromosome and on both female X-chromosomes. In fact, XCI occurs in males as characterised by appearance of a repressive chromatin signature and partial X-linked gene silencing, albeit transiently and rapidly. Likewise, in the embryo Xist is transiently expressed in males and in females from both X-chromosomes at the onset of epiblast differentiation. In conclusion, we propose that XCI initiation is gender independent and triggered by the destabilization of the naïve identity, which suggests that gender-specific mechanisms follow rather than precede XCI initiation.

2018-06-13 | GSE109173 | GEO

Reversion to naïve human pluripotency creates a new methylation landscape devoid of blastocyst or germline memory

Project description:Human embryonic stem cells (hESCs) typically exhibit "primed" pluripotency, analogous to stem cells derived from the mouse post-implantation epiblast. This has led to a search for growth conditions that support self-renewal of hESCs akin to hypomethylated naïve epiblast cells in human pre-implantation embryos. We have discovered that reverting primed hESCs to a hypomethylated naïve state or deriving a new hESC line under naïve conditions results in the establishment of Stage Specific Embryonic Antigen 4 (SSEA4) negative hESC lines with a transcriptional program resembling the human pre-implantation epiblast. In contrast, we discovered that the methylome of naïve hESCs in vitro is distinct from the human epiblast in vivo with loss of DNA methylation at primary imprints and a lost "memory" of the methylation state of the human oocyte. This failure to recover the naïve epiblast methylation landscape appears to be a consistent feature of self-renewing hypomethylated naïve hESCs in vitro.

2016-02-04 | GSE76970 | GEO

Project description:Inhibition of PRC2 enables self-renewal of naive pluripotent stem cells from chimpanzee

| PRJNA1086168 | ENA

PRC2 shields naïve human pluripotent cells from trophectoderm and mesoderm differentiation [scRNA-seq]

Project description:Single-cell RNA-seq reveals that Polycomb repressive complex 2 (PRC2) maintains naïve pluripotency and restricts an intrinsic capacity of pre-implantation pluripotent stem cells to give rise to trophectoderm and mesoderm lineages. Inhibition of PRC2 forces naïve hESC into an ‘activated’ state through which differentiation into either trophectoderm or mesoderm lineages is triggered. This trajectory is distinct from embryonic lineage specification out of the post-implantation pluripotent state, hence PRC2-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

2022-03-14 | GSE196280 | GEO

De novo formation of apical-basal polarity by Rap1 regulates epiblast patterning

Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.

2022-06-14 | PXD028315 | Pride

The PRC1 and PRC2 proximal interactome

Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC2 and PRC1, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. Interestingly, the EZH2 proxeome included both PRC complexes, while the RNF2 proxeome only identified PRC1 subunits. More than half of the PRC2 proximal proteins are shared with PRC1, revealing the molecular constitution of polycomb chromatin domains. We identified several pluripotency-associated transcription factors, including NANOG, for which we confirmed genomic co-localisation with PRC2. Upon PRC2 disruption, NANOG redistributes to specific sites containing its DNA binding motif. Finally, we compared PRC2 proximal interactomes between naïve mESCs, serum-cultured mESCs and embryoid bodies, altogether providing a comprehensive resource in different cellular contexts that may help to further decipher Polycomb biology.

2025-02-25 | PXD058327 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data