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Intracellular Ca2+ Homeostasis and Nuclear Export Mediate Exit from Naive Pluripotency.

ABSTRACT: Progression through states of pluripotency is required for cells in early mammalian embryos to transition away from heightened self-renewal and toward competency for lineage specification. Here, we use a CRISPR mutagenesis screen in mouse embryonic stem cells (ESCs) to identify unexpected roles for nuclear export and intracellular Ca2+ homeostasis during the exit out of the naive state of pluripotency. Mutation of a plasma membrane Ca2+ pump encoded by Atp2b1 increased intracellular Ca2+ such that it overcame effects of intracellular Ca2+ reduction, which is required for naive exit. Persistent self-renewal of ESCs was supported both in Atp2b1-/-Tcf7l1-/- double-knockout ESCs passaged in defined media alone (no LIF or inhibitors) and in wild-type cells passaged in media containing only calcitonin and a GSK3 inhibitor. These new findings suggest a central role for intracellular Ca2+ in safeguarding naive pluripotency.

SUBMITTER: MacDougall MS

PROVIDER: S-EPMC6685429 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Intracellular Ca2+ Homeostasis and Nuclear Export Mediate Exit from Naive Pluripotency.

MacDougall Matthew S MS Clarke Ryan R Merrill Bradley J BJ

Cell stem cell 20190516 2

Progression through states of pluripotency is required for cells in early mammalian embryos to transition away from heightened self-renewal and toward competency for lineage specification. Here, we use a CRISPR mutagenesis screen in mouse embryonic stem cells (ESCs) to identify unexpected roles for nuclear export and intracellular Ca2+ homeostasis during the exit out of the naive state of pluripotency. Mutation of a plasma membrane Ca2+ pump encoded by Atp2b1 increased intr ...[more]

PMID: 31104942

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