KLF17 promotes human naive pluripotency through repressing MAPK3 and ZIC2
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA801152 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human naïve ESCs cultured in RSET medium with KLF17 knockdown and human primed ESCs cultured in mTeSR with KLF17 overexpression were sequenced by poly(A)+RNA-seq.
2022-08-19 | GSE195535 | GEO
Project description:ZIC2 and ZIC3 are essential for acquisition and maintenance of primed pluripotency. In this study, we conducted ATAC-seq in single and compound knockout of ZIC2, ZIC3 and ZIC5 primed hESCs, naïve hESCs lacking ZIC3 that inducibly express ZIC2, naive hESCs that inducible express ZIC2 or ZIC3, ZIC3-depleted primed hESCs that were cultured in 5iLAF medium for six days and undergoing reversion to a naive state, naive hESCs expressing ectopic ZIC2 in the presence of a BRG1 PROTAC.
2024-08-20 | GSE270948 | GEO
Project description:Bulk RNA-seq of H9 human embryonic stem cells undergoing conversion from primed to naive pluripotency using the chemical/epigenetic resetting method in tt2iL+Go-based media conditions. The dataset includes three wild-type clones (WT1-3) and two KLF17-null clones (KO1-2) generated through CRISPR-Cas9-mediated gene editing. Samples were collected at day 0 (primed cells in mTeSR1 (StemCell Technologies)), then throughout resetting at day 2 (cells in cRM-1), day 8 (cells in cRM-2+XAV939, immediately prior to the first passage), naive passage 5 (p5), 7 (p7) and 10 (p10) (cells in tt2iL+Go).
2021-09-30 | E-MTAB-10914 | biostudies-arrayexpress
Project description:RNA-seq of H9 human embryonic stem cells cultured under naive pluripotency-supportive PXGL conditions either with (Dox) or without (UI) exogenous KLF17 expression for five days. As well as a day 0 control sample (hESCs 24hrs after plating in mTeSR), both UI and +Dox samples were collected at days 1, 2 and 5 after switching to naive-permissive PXGL culture conditions. Only Dox-induced hESCs survive after the first passage and form stable lines in PXGL with naive-like morphology and transcriptome, which could be maintained until naive passage 5 (p5).
2021-09-30 | E-MTAB-10915 | biostudies-arrayexpress
Project description:ZIC2 and ZIC3 are essential for acquisition and maintenance of primed pluripotency. In this study, we conducted next generation sequencing of polyA-enriched bulk RNA in single and compound knockouts of ZIC2, ZIC3 and ZIC5 primed hESCs, naïve hESCs lacking ZIC3 that inducibly express ZIC2, and primed hESCs that were cultured in 5iLAF medium for six days and undergoing reversion to a naive state.
2024-08-20 | GSE270786 | GEO
Project description:Pluripotency can be maintained in the naïve state through manipulation of ERK and WNT signalling (2i), shielding embryonic stem cells (ESCs) from inductive cues. Alternatively, inhibiting CDK8/19 (CDK8/19i), a repressor of the Mediator co-activator complex, directly stimulates super-enhancer activity, and was recently shown to stabilize cells in a functional state that resembles naïve pluripotency. Naïve ESCs exhibit important epigenetic, transcriptional and metabolic features. However, our understanding on how these regulatory layers are inter-connected to promote the naive state is in progress. To fill this gap, here we used mass spectrometry to describe the dynamic molecular events (i.e. phosphoproteome, proteome and metabolome) executed by 2i and CDK8/19i, as they transition cell identity into naïve pluripotency. We observed rapid proteomic reprogramming, revealing widespread commonalities, and some important differences, between these two approaches, suggesting a largely over-lapping mechanism. CDK8/19i acts directly on the control of the transcriptional machinery, which elicits a rapid and direct activation of key identity genes including those that maintain the naïve program. Additional molecular changes in 2i are achieved by phosphorylation of critical downstream effectors that reinforce the naïve transcriptional circuitry while repressing factors from the more-differentiated formative and primed states. Comparing transcriptomic and proteomic changes, we found that post-transcriptional de-repression is a major feature of naïve pluripotency conferred by both 2i and CDK8/19i, and this may support the enhanced mitochondrial capacity of naive cells. Furthermore, at the level of metabolome, while 2i- and CDK8/19i-treated cells share similar aspects in one-carbon metabolism and beta-oxidation, in other regards they are divergent, a feature which may explain their differences in DNA methylation. These datasets provide a valuable resource for exploring the molecular mechanisms underlying pluripotency and cell identity transitions.
2021-02-10 | PXD018694 | Pride
Project description:ZIC2 and ZIC3 are essential for acquisition and maintenance of primed pluripotency. In this study, we profiled chromatin occupancy of BRG1, EZH2, H3K27ac and H3K4me3 upon concomitant loss of ZIC2 and ZIC3 in primed hESCs, and of BRG1 upon ectopic expression of ZIC2 for increasing periods of time in naïve hESCs.
2024-08-20 | GSE270822 | GEO
Project description:The primed epiblast acts as a transitional stage between the relatively homogeneous naïve epiblast and the gastrulating embryo. Its formation entails coordinated changes in regulatory circuits driven by strict epigenetic mechanisms. Using a multi-omic approach in human embryonic stem cell models across the spectrum of peri-implantation development, we demonstrate that the transcription factors ZIC2 and ZIC3 have overlapping but essential roles in opening primed-specific enhancers. Together they are essential to facilitate progression to and maintain primed pluripotency. ZIC2/3 achieve their function by recruiting SWI/SNF to chromatin and loss of ZIC2/3 or degradation of SWI/SNF both prevent enhancer activation. Loss of ZIC2/3 results in transcriptome changes consistent with perturbed Polycomb activity and a shift towards the expression of genes linked to mesendoderm differentiation. Additionally, we find an intriguing dependency on the transcriptional machinery for sustained recruitment of ZIC2/3 over a subset of primed-hESC specific enhancers. Taken together, ZIC2 and ZIC3 regulate highly dynamic lineage-specific enhancers and collectively act as key regulators of human primed pluripotency.
2024-08-20 | GSE270784 | GEO
Project description:RNA-seq of wild-type and KLF17-null hESCs during chemical resetting from primed to naive pluripotency
| PRJEB47484 | 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