AMPK activation reverts mouse epiblast stem cells to naive state

Yajing Liu; Junko Yamane; Akito Tanaka; Wataru Fujibuchi; Jun K Yamashita

doi:10.1016/j.isci.2021.102783

AMPK activation reverts mouse epiblast stem cells to naive state

iScience. 2021 Jun 25;24(7):102783. doi: 10.1016/j.isci.2021.102783. eCollection 2021 Jul 23.

Authors

Yajing Liu¹, Junko Yamane², Akito Tanaka³, Wataru Fujibuchi², Jun K Yamashita¹

Affiliations

¹ The Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
² The Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
³ The Department of Animal Research Facility, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.

Abstract

Despite increasing knowledge on primed and naive pluripotency, the cell signaling that regulates the pluripotency type in stem cells remains not fully understood. Here we show that AMP kinase (AMPK) activators can induce the reversion of primed mouse epiblast stem cells (mEpiSCs) to the naive pluripotent state. The addition of AMPK activators alone or together with leukemia inhibitory factor to primed mEpiSCs induced the appearance of naive-like cells. After passaging in naive culture conditions, the colony morphology, protein expression, and global gene expression profiles indicated the naive state, as did germline transmission ability. Loss-of-function and gain-of-function studies suggested that p38 is a critical downstream target in AMPK activation. Finally, single-cell RNA sequencing analysis revealed that the reversion process through AMPK signaling passes an intermediate naive-like population. In conclusion, the AMPK pathway is a critical driving force in the reversion of primed to naive pluripotency.

Keywords: Cell biology; Stem cells research; Transcriptomics.