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Cell cycle states of pluripotent cells dictate lineage decisions

ABSTRACT: Cell cycle and differentiation decisions are tightly linked; however, the underlying principles that drive these decisions are not fully understood. Here, we combined cell-cycle reporter system and single-cell RNA-seq profiling, to study the transcriptomes of mouse embryonic stem cells (ESCs) in the context of cell cycle states and differentiation. By applying a retinoic acid-based differentiation protocol we show that only cells in the G2/M phase are capable of differentiating into extraembryonic endoderm cells (XENs), whereas cells in the G1 phase predominantly produce epiblast stem cells (EpiSCs). Mechanistically, we show that Esrrb is a potent XEN state inducer as it is predominantly upregulated during G2/M phase, and cells engineered to overexpress Esrrb during G1 phase forced the cells to become XENs. Interestingly, this phenomenon is unique to the pluripotency ground state as sorting cells after 48 hours of differentiation resulted in a cell cycle-independent differentiation decisions. Cells in both G1 and G2/M phases contributed equally to EpiSC and XEN cellular lineages. Taken together, this study reveals an important functional link between cell-cycle states of pluripotent cells and lineage decisions, emphasizing the regulatory role of cell cycle during exit from pluripotency and can be further expand our understanding of early differentiation events.

ORGANISM(S): Mus musculus

PROVIDER: GSE178390 | GEO | 2022/05/19

REPOSITORIES: GEO

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