miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells

Abstract Human induced pluripotent stem (hiPS) cells are feasible materials for studying the biological mechanisms underlying human embryogenesis. In early embryogenesis, definitive endoderm and mesoderm are differentiated from their common precursor, mesendoderm. Bone morphogenetic protein (BMP) si...

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Autores principales:	Jaeeun Lim, Eiko Sakai, Fuminori Sakurai, Hiroyuki Mizuguchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60aaa8f2f9fa4595922df2b46adea995
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spelling	oai:doaj.org-article:60aaa8f2f9fa4595922df2b46adea9952021-12-02T16:56:36ZmiR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells10.1038/s41598-021-99403-92045-2322https://doaj.org/article/60aaa8f2f9fa4595922df2b46adea9952021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99403-9https://doaj.org/toc/2045-2322Abstract Human induced pluripotent stem (hiPS) cells are feasible materials for studying the biological mechanisms underlying human embryogenesis. In early embryogenesis, definitive endoderm and mesoderm are differentiated from their common precursor, mesendoderm. Bone morphogenetic protein (BMP) signaling is responsible for regulating mesendoderm and mesoderm formation. Micro RNAs (miRNAs), short non-coding RNAs, broadly regulate biological processes via post-transcriptional repression. The expression of miR-27b, which is enriched in somatic cells, has been reported to increase through definitive endoderm and hepatic differentiation, but little is known about how miR-27b acts during early differentiation. Here, we used miR-27b-inducible hiPS cells to investigate the roles of miR-27b in the undifferentiated and early-differentiated stages. In undifferentiated hiPS cells, miR-27b suppressed the expression of pluripotency markers [alkaline phosphatase (AP) and nanog homeobox (NANOG)] and cell proliferation. Once differentiation began, miR-27b expression repressed phosphorylated SMAD1/5, the mediators of the BMP signaling, throughout definitive endoderm differentiation. Consistent with the above findings, miR-27b overexpression downregulated BMP-induced mesendodermal marker genes [Brachyury, mix paired-like homeobox 1 (MIXL1) and eomesodermin (EOMES)], suggesting that miR-27b had an inhibitory effect on early differentiation. Collectively, our findings revealed a novel antagonistic role of miR-27b in the BMP signaling pathway in the early differentiation of hiPS cells.Jaeeun LimEiko SakaiFuminori SakuraiHiroyuki MizuguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jaeeun Lim Eiko Sakai Fuminori Sakurai Hiroyuki Mizuguchi miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells
description	Abstract Human induced pluripotent stem (hiPS) cells are feasible materials for studying the biological mechanisms underlying human embryogenesis. In early embryogenesis, definitive endoderm and mesoderm are differentiated from their common precursor, mesendoderm. Bone morphogenetic protein (BMP) signaling is responsible for regulating mesendoderm and mesoderm formation. Micro RNAs (miRNAs), short non-coding RNAs, broadly regulate biological processes via post-transcriptional repression. The expression of miR-27b, which is enriched in somatic cells, has been reported to increase through definitive endoderm and hepatic differentiation, but little is known about how miR-27b acts during early differentiation. Here, we used miR-27b-inducible hiPS cells to investigate the roles of miR-27b in the undifferentiated and early-differentiated stages. In undifferentiated hiPS cells, miR-27b suppressed the expression of pluripotency markers [alkaline phosphatase (AP) and nanog homeobox (NANOG)] and cell proliferation. Once differentiation began, miR-27b expression repressed phosphorylated SMAD1/5, the mediators of the BMP signaling, throughout definitive endoderm differentiation. Consistent with the above findings, miR-27b overexpression downregulated BMP-induced mesendodermal marker genes [Brachyury, mix paired-like homeobox 1 (MIXL1) and eomesodermin (EOMES)], suggesting that miR-27b had an inhibitory effect on early differentiation. Collectively, our findings revealed a novel antagonistic role of miR-27b in the BMP signaling pathway in the early differentiation of hiPS cells.
format	article
author	Jaeeun Lim Eiko Sakai Fuminori Sakurai Hiroyuki Mizuguchi
author_facet	Jaeeun Lim Eiko Sakai Fuminori Sakurai Hiroyuki Mizuguchi
author_sort	Jaeeun Lim
title	miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells
title_short	miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells
title_full	miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells
title_fullStr	miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells
title_full_unstemmed	miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells
title_sort	mir-27b antagonizes bmp signaling in early differentiation of human induced pluripotent stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/60aaa8f2f9fa4595922df2b46adea995
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miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells

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