Artificial induction of circadian rhythm by combining exogenous BMAL1 expression and polycomb repressive complex 2 inhibition in human induced pluripotent stem cells.


Journal

Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402

Informations de publication

Date de publication:
08 Jul 2023
Historique:
received: 15 03 2023
accepted: 26 06 2023
revised: 22 06 2023
medline: 10 7 2023
pubmed: 8 7 2023
entrez: 8 7 2023
Statut: epublish

Résumé

Understanding the physiology of human-induced pluripotent stem cells (iPSCs) is necessary for directed differentiation, mimicking embryonic development, and regenerative medicine applications. Pluripotent stem cells (PSCs) exhibit unique abilities such as self-renewal and pluripotency, but they lack some functions that are associated with normal somatic cells. One such function is the circadian oscillation of clock genes; however, whether or not PSCs demonstrate this capability remains unclear. In this study, the reason why circadian rhythm does not oscillate in human iPSCs was examined. This phenomenon may be due to the transcriptional repression of clock genes resulting from the hypermethylation of histone H3 at lysine 27 (H3K27), or it may be due to the low levels of brain and muscle ARNT-like 1 (BMAL1) protein. Therefore, BMAL1-overexpressing cells were generated and pre-treated with GSK126, an inhibitor of enhancer of zest homologue 2 (EZH2), which is a methyltransferase of H3K27 and a component of polycomb repressive complex 2. Consequently, a significant circadian rhythm following endogenous BMAL1, period 2 (PER2), and other clock gene expression was induced by these two factors, suggesting a candidate mechanism for the lack of rhythmicity of clock gene expression in iPSCs.

Identifiants

pubmed: 37421441
doi: 10.1007/s00018-023-04847-z
pii: 10.1007/s00018-023-04847-z
doi:

Substances chimiques

ARNTL Transcription Factors 0
CLOCK Proteins EC 2.3.1.48
Polycomb Repressive Complex 2 EC 2.1.1.43
BMAL1 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

200

Subventions

Organisme : Japan Society for the Promotion of Science
ID : JP18K06876
Organisme : Japan Science and Technology Corporation
ID : JPMJTM19GL

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Hitomi Kaneko (H)

Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan.

Taku Kaitsuka (T)

School of Pharmacy at Fukuoka, International University of Health and Welfare, Enokizu 137-1, Okawa, Fukuoka, 831-8501, Japan. kaitsuka@iuhw.ac.jp.

Kazuhito Tomizawa (K)

Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan. tomikt@kumamoto-u.ac.jp.

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