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A transcriptional roadmap for 2C-like to pluripotent state transition [single cells]

ABSTRACT: A transcriptional roadmap for 2C-like to pluripotent state transition [single cells]

PROVIDER: PRJNA550426 | ENA |

REPOSITORIES: ENA

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A transcriptional roadmap for 2C-like to pluripotent state transition

Project description:A transcriptional roadmap for 2C-like to pluripotent state transition

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A transcriptional roadmap for 2C-like to pluripotent state transition [single cells]

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.

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A transcriptional roadmap for 2C-like to pluripotent state transition [bulk RNA]

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RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly

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Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells (RNA-Seq)

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.

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Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells (ChIP-Seq)

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A transcriptional roadmap for 2C-like-to-pluripotent state transition.

Project description:In mouse embryonic stem cell (ESC), a small cell population displays totipotent features by expressing a set of genes that are transiently active in 2-cell-stage embryos. These 2-cell-like (2C-like) cells spontaneously transit back into the pluripotent state. We previously dissected the transcriptional dynamics of the transition from pluripotency to the totipotent 2C-like state and identified factors that modulate the process. However, how 2C-like cells transit back into the pluripotent state remains largely unknown. In this study, we analyzed the transcriptional dynamics from the 2C-like state to pluripotent ESCs and identified an intermediate state. The intermediate state characterized by two-wave step up-regulation of pluripotent genes is different from the one observed during the 2C-like entry transition. Nonsense-mediated Dux mRNA decay plays an important role in the 2C-like state exit. Thus, our study not only provides a transcriptional roadmap for 2C-like-to-pluripotent state transition but also reveals a key molecular event driving the transition.

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RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (RNA-Seq)

Project description:RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (RNA-Seq)

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Project description:RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (Mnase-Seq)

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