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 inhibit

SUBMITTER: MacDougall MS 

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

REPOSITORIES: biostudies-literature