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AMPK activation reverts mouse epiblast stem cells to naive state
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 plurip...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283141/ https://www.ncbi.nlm.nih.gov/pubmed/34308289 http://dx.doi.org/10.1016/j.isci.2021.102783 |
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author | Liu, Yajing Yamane, Junko Tanaka, Akito Fujibuchi, Wataru Yamashita, Jun K. |
author_facet | Liu, Yajing Yamane, Junko Tanaka, Akito Fujibuchi, Wataru Yamashita, Jun K. |
author_sort | Liu, Yajing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8283141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82831412021-07-22 AMPK activation reverts mouse epiblast stem cells to naive state Liu, Yajing Yamane, Junko Tanaka, Akito Fujibuchi, Wataru Yamashita, Jun K. iScience Article 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. Elsevier 2021-06-25 /pmc/articles/PMC8283141/ /pubmed/34308289 http://dx.doi.org/10.1016/j.isci.2021.102783 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yajing Yamane, Junko Tanaka, Akito Fujibuchi, Wataru Yamashita, Jun K. AMPK activation reverts mouse epiblast stem cells to naive state |
title | AMPK activation reverts mouse epiblast stem cells to naive state |
title_full | AMPK activation reverts mouse epiblast stem cells to naive state |
title_fullStr | AMPK activation reverts mouse epiblast stem cells to naive state |
title_full_unstemmed | AMPK activation reverts mouse epiblast stem cells to naive state |
title_short | AMPK activation reverts mouse epiblast stem cells to naive state |
title_sort | ampk activation reverts mouse epiblast stem cells to naive state |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283141/ https://www.ncbi.nlm.nih.gov/pubmed/34308289 http://dx.doi.org/10.1016/j.isci.2021.102783 |
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