Similar Datasets
Project description:Mouse ESCs and EpiSCs represent naive and primed states of plurioptency corresponding to two consecutive stages of embryo development. Here we map their chromatin accessibility landscapes and show that naive specific open chromatin are enriched with motifs for Oct/Sox/Klf/TCF and primed one with AP1 motifs. The AP1 founding member c-Jun is expressed in EpiSCs and occupies both open and closed chromatin. Yet, c-Jun deficiency has no impact on the self renewal nor the transcription program of EpiSCs. However, in a Klf4-driven reprogramming system, we show that c-Jun-/- EpiSCs undergo primed to naive transition more efficiently than wild type cells and Klf4 evicts c-JUN from wild type chromatin. These results suggest that c-Jun is a pioneer factor not to regulate transcription but to prevent backward reprogramming during naive-primed transition, thus providing a molecular basis for the forward principle in development.
2020-12-31 | GSE127925 | GEO
Project description:Mouse ESCs and EpiSCs represent naive and primed states of plurioptency corresponding to two consecutive stages of embryo development. Here we map their chromatin accessibility landscapes and show that naive specific open chromatin are enriched with motifs for Oct/Sox/Klf/TCF and primed one with AP1 motifs. The AP1 founding member c-Jun is expressed in EpiSCs and occupies both open and closed chromatin. Yet, c-Jun deficiency has no impact on the self renewal nor the transcription program of EpiSCs. However, in a Klf4-driven reprogramming system, we show that c- Jun-/- EpiSCs undergo primed to naive transition more efficiently than wild type cells and Klf4 evicts c-JUN from wild type chromatin. These results suggest that c-Jun is a pioneer factor not to regulate transcription but to prevent backward reprogramming during naive-primed transition, thus providing a molecular basis for the forward principle in development.
2020-12-31 | GSE127921 | GEO
Project description:Mouse ESCs and EpiSCs represent naive and primed states of plurioptency corresponding to two consecutive stages of embryo development. Here we map their chromatin accessibility landscapes and show that naive specific open chromatin are enriched with motifs for Oct/Sox/Klf/TCF and primed one with AP1 motifs. The AP1 founding member c-Jun is expressed in EpiSCs and occupies both open and closed chromatin. Yet, c-Jun deficiency has no impact on the self renewal nor the transcription program of EpiSCs. However, in a Klf4-driven reprogramming system, we show that c- Jun-/- EpiSCs undergo primed to naive transition more efficiently than wild type cells and Klf4 evicts c-JUN from wild type chromatin. These results suggest that c-Jun is a pioneer factor not to regulate transcription but to prevent backward reprogramming during naive-primed transition, thus providing a molecular basis for the forward principle in development.
2020-12-31 | GSE127920 | GEO
Project description:During development, human primordial germ cells (hPGCs) transition through a transcriptional and epigenetic state similar to pre-implantation epiblast cells called naive ground-state pluripotency. Diagnostic transcription factors that define this state include TFAP2C, KLF4, and TFCP2L1, with TFAP2C necessary for both establishment of the naive-like state in hPGC-like cells (hPGCLCs) as well as establishment and self-renewal of naive human embryonic stem cells (hESCs). Here, we show that KLF4 and TFCP2L1 are not required for hPGC specification or establishment of the naive-like state in hPGCLCs. Instead, KLF4 and TFCP2L1 are each required for reversion of primed hESCs to the self-renewing naive ground state. Additionally, TFCP2L1 but not KLF4 function after hPGC specification in the proliferation of the hPGCLC population.
2022-04-30 | GSE148717 | GEO
Project description:Human pluripotent stem cells have two major pluripotent states, primed and naive, and the heterogeneity among cell lines in each pluripotent state remains a major unresolved problem. We showed that the overexpression of H1FOO-DD, which has a short expression period by fusing the destabilized domain to the maternal-specific linker histone H1FOO, together with OCT4, SOX2, KLF4 and LMYC in human somatic cells improves the quality of reprogramming to primed and naive pluripotency.
2024-05-01 | GSE253926 | GEO
Project description:Human pluripotent stem cells have two major pluripotent states, primed and naive, and the heterogeneity among cell lines in each pluripotent state remains a major unresolved problem. We showed that the overexpression of H1FOO-DD, which has a short expression period by fusing the destabilized domain to the maternal-specific linker histone H1FOO, together with OCT4, SOX2, KLF4 and LMYC in human somatic cells improves the quality of reprogramming to primed and naive pluripotency.
2024-05-01 | GSE224700 | GEO
Project description:Human pluripotent stem cells have two major pluripotent states, primed and naive, and the heterogeneity among cell lines in each pluripotent state remains a major unresolved problem. We showed that the overexpression of H1FOO-DD, which has a short expression period by fusing the destabilized domain to the maternal-specific linker histone H1FOO, together with OCT4, SOX2, KLF4 and LMYC in human somatic cells improves the quality of reprogramming to primed and naive pluripotency.
2024-05-01 | GSE224699 | GEO
Project description:Human pluripotent stem cells have two major pluripotent states, primed and naive, and the heterogeneity among cell lines in each pluripotent state remains a major unresolved problem. We showed that the overexpression of H1FOO-DD, which has a short expression period by fusing the destabilized domain to the maternal-specific linker histone H1FOO, together with OCT4, SOX2, KLF4 and LMYC in human somatic cells improves the quality of reprogramming to primed and naive pluripotency.
2024-05-01 | GSE224698 | GEO
Project description:Human pluripotent stem cells have two major pluripotent states, primed and naive, and the heterogeneity among cell lines in each pluripotent state remains a major unresolved problem. We showed that the overexpression of H1FOO-DD, which has a short expression period by fusing the destabilized domain to the maternal-specific linker histone H1FOO, together with OCT4, SOX2, KLF4 and LMYC in human somatic cells improves the quality of reprogramming to primed and naive pluripotency.
2024-05-01 | GSE224697 | GEO
Project description:Human pluripotent stem cells (hPSCs) serve as powerful in vitro models to elucidate the molecular underpinnings of embryonic cell fate transitions. hPSCs can be maintained in two distinct states: a naïve state, corresponding to the pre-implantation epiblast, and a primed state, mirroring the post-implantation epiblast. Our research demonstrates that transposable elements act as sensitive indicators of these pluripotency states. We engineered hPSCs with fluorescent reporters that capture the temporal expression dynamics of two transposable elements, LTR5_Hs and MER51B. This dual reporter system facilitates real-time monitoring and isolation of stem cells as they transition from naïve to primed pluripotency and further towards differentiation. Unexpectedly, we identified a rare, metastable cell population within primed hPSCs, marked by transcripts associated with pre-implantation embryo development and triggered by DNA damage. Additionally, our system uncovered novel transcriptional regulators involved in pluripotency, naïve reprogramming, and differentiation. Our study provides key insights into the dynamic regulation of transposable elements during embryonic development and introduces a novel system for investigating and exploiting cellular plasticity.
2024-11-01 | GSE272118 | GEO