Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density

Abstract Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differen...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Minh Nguyen Tuyet Le, Mika Takahi, Kiyoshi Ohnuma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a98de90680ac4ff5928fcd7d0400986f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a98de90680ac4ff5928fcd7d0400986f
record_format	dspace
spelling	oai:doaj.org-article:a98de90680ac4ff5928fcd7d0400986f2021-11-08T10:46:12ZAuto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density10.1038/s41598-021-00763-z2045-2322https://doaj.org/article/a98de90680ac4ff5928fcd7d0400986f2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00763-zhttps://doaj.org/toc/2045-2322Abstract Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differentiation. Previously, we established a protocol to induce hiPSC differentiation into cardiomyocytes using a defined culture medium and an initial low cell density (1% confluence) to minimize the hidden factors. Here, we investigated the key factors promoting cardiomyocyte differentiation at an initial low cell density to clarify the effects of cell density. Co-culture of hiPSCs at an initial low cell density with those at an initial high cell density showed that signals secreted from cells (auto/paracrine factors) and not cell–cell contact signals, played an important role in cardiomyocyte differentiation. Moreover, although cultures with initial low cell density showed higher expression of anti-cardiac mesoderm genes, earlier treatment with a Wnt production inhibitor efficiently suppressed the anti-cardiac mesoderm gene expression and promoted cardiomyocyte differentiation by up to 80% at an initial low cell density. These results suggest that the main effect of cell density on cardiomyocyte differentiation is inhibition of Wnt signaling at the early stage of induction, through auto/paracrine factors.Minh Nguyen Tuyet LeMika TakahiKiyoshi OhnumaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Minh Nguyen Tuyet Le Mika Takahi Kiyoshi Ohnuma Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
description	Abstract Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differentiation. Previously, we established a protocol to induce hiPSC differentiation into cardiomyocytes using a defined culture medium and an initial low cell density (1% confluence) to minimize the hidden factors. Here, we investigated the key factors promoting cardiomyocyte differentiation at an initial low cell density to clarify the effects of cell density. Co-culture of hiPSCs at an initial low cell density with those at an initial high cell density showed that signals secreted from cells (auto/paracrine factors) and not cell–cell contact signals, played an important role in cardiomyocyte differentiation. Moreover, although cultures with initial low cell density showed higher expression of anti-cardiac mesoderm genes, earlier treatment with a Wnt production inhibitor efficiently suppressed the anti-cardiac mesoderm gene expression and promoted cardiomyocyte differentiation by up to 80% at an initial low cell density. These results suggest that the main effect of cell density on cardiomyocyte differentiation is inhibition of Wnt signaling at the early stage of induction, through auto/paracrine factors.
format	article
author	Minh Nguyen Tuyet Le Mika Takahi Kiyoshi Ohnuma
author_facet	Minh Nguyen Tuyet Le Mika Takahi Kiyoshi Ohnuma
author_sort	Minh Nguyen Tuyet Le
title	Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
title_short	Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
title_full	Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
title_fullStr	Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
title_full_unstemmed	Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
title_sort	auto/paracrine factors and early wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a98de90680ac4ff5928fcd7d0400986f
work_keys_str_mv	AT minhnguyentuyetle autoparacrinefactorsandearlywntinhibitionpromotecardiomyocytedifferentiationfromhumaninducedpluripotentstemcellsatinitiallowcelldensity AT mikatakahi autoparacrinefactorsandearlywntinhibitionpromotecardiomyocytedifferentiationfromhumaninducedpluripotentstemcellsatinitiallowcelldensity AT kiyoshiohnuma autoparacrinefactorsandearlywntinhibitionpromotecardiomyocytedifferentiationfromhumaninducedpluripotentstemcellsatinitiallowcelldensity
_version_	1718442650031357952

Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density

Ejemplares similares