A transcriptional roadmap for 2C-like to pluripotent state transition
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ABSTRACT:
PROVIDER: PRJNA550421 | ENA |
REPOSITORIES: ENA
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Project description:In mouse embryonic stem cell (ESC) culture, a small proportion of cells display totipotent features by expressing a set of genes that are only active in 2-cell-stage embryos. These 2-cell-like (2C-like) cells spontaneously transit back into pluripotent state. We previously dissected the transcriptional dynamics of pluripotent to 2C-like transition and identified factors that modulate the transition. However, how 2C-like cells transits back to the pluripotent state and what factors drive this process remains largely unknown. To address these questions, we examined the transcriptional dynamics during the reverse transition from the 2C-like state to ESCs and identified an intermediate state involved in the transition. Interestingly, we found that mESCs exit from the 2C-like state through a molecular path characterized by a two-wave upregulation of pluripotent genes different from the one observed during the 2C-like entry transition. We also showed that nonsense-mediated mRNA decay (NMD) targets Dux mRNA and affects 2C-like state maintenance, suggesting that Dux degradation contributes to the reversal of 2C-like state.
2020-03-20 | GSE133233 | GEO
Project description:In mouse embryonic stem cell (ESC) culture, a small proportion of cells display totipotent features by expressing a set of genes that are only active in 2-cell-stage embryos. These 2-cell-like (2C-like) cells spontaneously transit back into pluripotent state. We previously dissected the transcriptional dynamics of pluripotent to 2C-like transition and identified factors that modulate the transition. However, how 2C-like cells transits back to the pluripotent state and what factors drive this process remains largely unknown. To address these questions, we examined the transcriptional dynamics during the reverse transition from the 2C-like state to ESCs and identified an intermediate state involved in the transition. Interestingly, we found that mESCs exit from the 2C-like state through a molecular path characterized by a two-wave upregulation of pluripotent genes different from the one observed during the 2C-like entry transition. We also showed that nonsense-mediated mRNA decay (NMD) targets Dux mRNA and affects 2C-like state maintenance, suggesting that Dux degradation contributes to the reversal of 2C-like state.
2020-03-20 | GSE133232 | GEO
Project description:A transcriptional roadmap for 2C-like to pluripotent state transition [bulk RNA]
| PRJNA550425 | ENA
Project description:A transcriptional roadmap for 2C-like to pluripotent state transition [single cells]
| PRJNA550426 | ENA
Project description:Mouse embryonic stem cells (ESCs) show cell-to-cell heterogeneity. A small fraction of 2-cell-like cells (2CLCs) marked by endogenous retrovirus activation emerge spontaneously. The 2CLCs are instable and they transit back to the pluripotent state without extrinsic stimulus. To understand how this bidirectional transition takes place, we performed single-cell RNA-seq on isolated 2CLCs which underwent 2C-like state exit and re-entry, and revealed a novel circular transitional process between 2C-like and pluripotent states. Mechanistically, we found that the cell cycle played an important role in mediating these transitions by regulating assembly of nucleolus and peri-nucleolar heterochromatin to influence 2C gene Dux expression. Collectively, our findings provide a roadmap of the 2C-like state entry and exit in ESCs and also a causal role of the cell cycle in promoting these transitions.
2021-04-01 | GSE171257 | GEO
Project description:Mouse embryonic stem cells (ESCs) show cell-to-cell heterogeneity. A small fraction of 2-cell-like cells (2CLCs) marked by endogenous retrovirus activation emerge spontaneously. The 2CLCs are instable and they transit back to the pluripotent state without extrinsic stimulus. To understand how this bidirectional transition takes place, we performed single-cell RNA-seq on isolated 2CLCs which underwent 2C-like state exit and re-entry, and revealed a novel circular transitional process between 2C-like and pluripotent states. Mechanistically, we found that the cell cycle played an important role in mediating these transitions by regulating assembly of nucleolus and peri-nucleolar heterochromatin to influence 2C gene Dux expression. Collectively, our findings provide a roadmap of the 2C-like state entry and exit in ESCs and also a causal role of the cell cycle in promoting these transitions.
2021-04-01 | GSE171258 | GEO
Project description: Not available
| S-EPMC7259939 | biostudies-literature
Project description:Cellular totipotency is critical for generating a whole organism, yet how to establish totipotency is still poorly illustrated. Unlike pluripotent stem cells, abundant transposable elements (TEs) are activated in the totipotent cells. Here, we show that histone chaperone RBBP4 but not its homologous RBBP7 is indispensable in maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms pluripotent state to a totipotent-like (also known as 2C-like) state. Mechanistically, RBBP4 could recruit G9a and KAP1 to bind on retrotransposons, especially endogenous retroviruses. RBBP4 degradation reduces the binding of G9a-mediated H3K9me2 on ERVL (particularly MERVL) and KAP1-mediated H3K9me3 on ERV1/ERVK, respectively. Moreover, RBBP4 facilitates nucleosome occupancy through chromatin remodeler CHD4 and RBBP4 depletion leads to attenuation of CHD4 binding and nucleosome occupancy on TEs. Together, our study reveals the important roles of RBBP4 in heterochromatin assembly and its loss activates TEs in mESCs, opening a new way to obtain totipotent cells in vitro.
2023-03-15 | GSE218653 | GEO
Project description:Cellular totipotency is critical for generating a whole organism, yet how to establish totipotency is still poorly illustrated. Unlike pluripotent stem cells, abundant transposable elements (TEs) are activated in the totipotent cells. Here, we show that histone chaperone RBBP4 but not its homologous RBBP7 is indispensable in maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms pluripotent state to a totipotent-like (also known as 2C-like) state. Mechanistically, RBBP4 could recruit G9a and KAP1 to bind on retrotransposons, especially endogenous retroviruses. RBBP4 degradation reduces the binding of G9a-mediated H3K9me2 on ERVL (particularly MERVL) and KAP1-mediated H3K9me3 on ERV1/ERVK, respectively. Moreover, RBBP4 facilitates nucleosome occupancy through chromatin remodeler CHD4 and RBBP4 depletion leads to attenuation of CHD4 binding and nucleosome occupancy on TEs. Together, our study reveals the important roles of RBBP4 in heterochromatin assembly and its loss activates TEs in mESCs, opening a new way to obtain totipotent cells in vitro.
2023-03-15 | GSE218654 | GEO
Project description:Cellular totipotency is critical for generating a whole organism, yet how to establish totipotency is still poorly illustrated. Unlike pluripotent stem cells, abundant transposable elements (TEs) are activated in the totipotent cells. Here, we show that histone chaperone RBBP4 but not its homologous RBBP7 is indispensable in maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms pluripotent state to a totipotent-like (also known as 2C-like) state. Mechanistically, RBBP4 could recruit G9a and KAP1 to bind on retrotransposons, especially endogenous retroviruses. RBBP4 degradation reduces the binding of G9a-mediated H3K9me2 on ERVL (particularly MERVL) and KAP1-mediated H3K9me3 on ERV1/ERVK, respectively. Moreover, RBBP4 facilitates nucleosome occupancy through chromatin remodeler CHD4 and RBBP4 depletion leads to attenuation of CHD4 binding and nucleosome occupancy on TEs. Together, our study reveals the important roles of RBBP4 in heterochromatin assembly and its loss activates TEs in mESCs, opening a new way to obtain totipotent cells in vitro.
2023-03-15 | GSE218655 | GEO