Name: Coordinated miRNA activity mediates the cellular transition into dormancy during embryonic diapause
Keywords: Embryonic diapause

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Coordinated miRNA activity mediates the cellular transition into dormancy during embryonic diapause

ABSTRACT: Dormancy is a key feature of stem cell function in adult tissues as well as embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state is not known. Here we show that microRNA activity, which is normally dispensable for pre-implantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in loss of pluripotency and embryo collapse. Through tissue-specific small RNA profiling of single embryos and computational analyses of miRNA targets, we identified the miRNA-protein network of diapause. Individual miRNA function contributes to combinatorial regulation by the network of most notably RNA processing and chromatin modifier proteins. Without miRNAs, multiple nuclear and cytoplasmic bodies show aberrant expression and structure in normal ESCs and fail to reorganize in response to stress. We find extensive alternative splicing in wild-type, but not miRNA-deficient ESCs, of cell cycle and metabolic regulators. Our results reveal that miRNAs are critical for the transcriptional and structural rewiring of pluripotent cells in response to stress and to establish dormancy in the pluripotent state.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: David Meierhofer

LAB HEAD: Aydan Bulut-Karslioglu

PROVIDER: PXD044550 | Pride | 2024-03-26

REPOSITORIES: Pride

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