Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA393617 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Overexpression of nuclear receptor 5A1 induces and maintains an intermediate state of conversion between primed and naive pluripotency
| PRJNA393693 | ENA
Project description:Overexpression of nuclear receptor 5A1 induces and maintains an intermediate state of conversion between primed and naive pluripotency
| PRJNA393695 | ENA
Project description:Overexpression of nuclear receptor 5A1 induces and maintains an intermediate state of conversion between primed and naive pluripotency
| PRJNA393696 | ENA
Project description:Naive and primed human pluripotent stem cells (hPSCs) have provided useful insights into the regulation of pluripotency. However, the molecular mechanisms regulating naive conversion remain elusive. Here, we report intermediate naive conversion induced by overexpressing nuclear receptor 5A1 (NR5A1) in hPSCs. The cells displayed some naive features, such as clonogenicity, glycogen synthase kinase 3β and mitogen activated protein kinase (MAPK) independence, expression of naive-associated genes, and two activated X chromosomes, but lacked others such as KLF17 expression, transforming growth factor β independence, and imprinted gene demethylation. Notably, NR5A1 negated MAPK activation by fibroblast growth factor 2, leading to cell-autonomous self-renewal independent of MAPK inhibition. These phenotypes may be associated with naive conversion, and were regulated by a DPPA2/4-dependent pathway that activates the selective expression of naive-associated genes. This study increases our understanding of the mechanisms regulating the conversion from primed to naive pluripotency.
2020-02-22 | GSE101088 | GEO
Project description:Naive and primed human pluripotent stem cells (hPSCs) have provided useful insights into the regulation of pluripotency. However, the molecular mechanisms regulating naive conversion remain elusive. Here, we report intermediate naive conversion induced by overexpressing nuclear receptor 5A1 (NR5A1) in hPSCs. The cells displayed some naive features, such as clonogenicity, glycogen synthase kinase 3β and mitogen activated protein kinase (MAPK) independence, expression of naive-associated genes, and two activated X chromosomes, but lacked others such as KLF17 expression, transforming growth factor β independence, and imprinted gene demethylation. Notably, NR5A1 negated MAPK activation by fibroblast growth factor 2, leading to cell-autonomous self-renewal independent of MAPK inhibition. These phenotypes may be associated with naive conversion, and were regulated by a DPPA2/4-dependent pathway that activates the selective expression of naive-associated genes. This study increases our understanding of the mechanisms regulating the conversion from primed to naive pluripotency.
2020-02-22 | GSE101087 | GEO
Project description:Naive and primed human pluripotent stem cells (hPSCs) have provided useful insights into the regulation of pluripotency. However, the molecular mechanisms regulating naive conversion remain elusive. Here, we report intermediate naive conversion induced by overexpressing nuclear receptor 5A1 (NR5A1) in hPSCs. The cells displayed some naive features, such as clonogenicity, glycogen synthase kinase 3β and mitogen activated protein kinase (MAPK) independence, expression of naive-associated genes, and two activated X chromosomes, but lacked others such as KLF17 expression, transforming growth factor β independence, and imprinted gene demethylation. Notably, NR5A1 negated MAPK activation by fibroblast growth factor 2, leading to cell-autonomous self-renewal independent of MAPK inhibition. These phenotypes may be associated with naive conversion, and were regulated by a DPPA2/4-dependent pathway that activates the selective expression of naive-associated genes. This study increases our understanding of the mechanisms regulating the conversion from primed to naive pluripotency.
2020-02-22 | GSE101043 | GEO
Project description:Naive pluripotent cells in the implanting mouse blastocyst generate a rosette structure before undergoing lumenogenesis to form the egg cylinder. Simultaneously, they acquire primed pluripotency, the ability to differentiate into the primary germ layers. The existence of discrete intermediate pluripotent states during this transition has not been demonstrated. We identify here a distinct rosette pluripotent state, defined by co-expression of naive factors with transcription factor OTX2. Downregulation of WNT signals in the blastocyst drives transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells (RSCs), a self-renewing naive-primed intermediate. RSCs gain a unique epigenome that includes erasure of constitutive heterochromatin and bivalent marking of primed pluripotency genes. Notwithstanding this primed chromatin landscape, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate where control over pluripotency progression and morphogenesis pivots from WNT to MEK signals.
2020-04-28 | GSE145726 | GEO
Project description:Naive pluripotent cells in the implanting mouse blastocyst generate a rosette structure before undergoing lumenogenesis to form the egg cylinder. Simultaneously, they acquire primed pluripotency, the ability to differentiate into the primary germ layers. The existence of discrete intermediate pluripotent states during this transition has not been demonstrated. We identify here a distinct rosette pluripotent state, defined by co-expression of naive factors with transcription factor OTX2. Downregulation of WNT signals in the blastocyst drives transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells (RSCs), a self-renewing naive-primed intermediate. RSCs gain a unique epigenome that includes erasure of constitutive heterochromatin and bivalent marking of primed pluripotency genes. Notwithstanding this primed chromatin landscape, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate where control over pluripotency progression and morphogenesis pivots from WNT to MEK signals.
2020-04-28 | GSE105762 | GEO
Project description:Upon implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked, and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state, defined by co-expression of naive factors with transcription factor OTX2. Downregulation of blastocyst WNT signals drives transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells (RSCs), a self-renewing naive-primed intermediate. RSCs erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate where control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.
2020-04-28 | GSE112234 | GEO
Project description:Mouse embryonic stem cells (mESCs) are in naive pluripotency that represents the ground state of development, from which all cells in the mouse embryo are derived. In contrast, human embryonic stem cells (hESCs) are in a primed state of pluripotency with many different properties. Despite intense efforts to generate naive human pluripotent stem cells (hPSCs), it has not been possible to derive naive hPSCs without relying on transgene overexpression or chemicals. Here, we show that a transient treatment with Torin1, a selective inhibitor of mTOR, converted hPSCs from primed to naive pluripotency. The naive hPSCs were maintained in the same condition as mESCs in defined media with 2iLI (MEK inhibitor, GSK3b inhibitor, LIF and Insulin). Like mESCs, they exhibited high clonal efficiency, rapid cell proliferation, active mitochondrial respiration, X chromosome activation, DNA hypomethylation, and transcriptomes similar to those of human blastocysts than primed hESCs. Most importantly, the naive hPSCs significantly contributed to mouse embryos when transferred to mouse blastocysts. mTor inhibition induced nuclear translocation of TFE3, a critical transcription factor at the interplay of autophagy and pluripotency. TFE3 with mutated nuclear localization signal blocked the conversion from primed to naive pluripotency. It appears that by mimicking diapause at the cellular level, naive pluripotency in human can be readily attained from primed hPSCs, thus establishing the unified ground state of pluripotency in mammals.
2020-05-13 | GSE102031 | GEO