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SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation

Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation...

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Autores principales: Kuroda, Takuya, Yasuda, Satoshi, Tachi, Shiori, Matsuyama, Satoko, Kusakawa, Shinji, Tano, Keiko, Miura, Takumi, Matsuyama, Akifumi, Sato, Yoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520385/
https://www.ncbi.nlm.nih.gov/pubmed/31092818
http://dx.doi.org/10.1038/s41467-019-09511-4
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author Kuroda, Takuya
Yasuda, Satoshi
Tachi, Shiori
Matsuyama, Satoko
Kusakawa, Shinji
Tano, Keiko
Miura, Takumi
Matsuyama, Akifumi
Sato, Yoji
author_facet Kuroda, Takuya
Yasuda, Satoshi
Tachi, Shiori
Matsuyama, Satoko
Kusakawa, Shinji
Tano, Keiko
Miura, Takumi
Matsuyama, Akifumi
Sato, Yoji
author_sort Kuroda, Takuya
collection PubMed
description Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlates positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. Without affecting self-renewal of hiPSCs, SALL3 knockdown inhibits ectoderm differentiation and conversely enhances mesodermal/endodermal differentiation. Similarly, loss- and gain-of-function studies reveal that SALL3 inversely regulates the differentiation of hiPSCs into cardiomyocytes and neural cells. Mechanistically, SALL3 modulates DNMT3B function and DNA methyltransferase activity, and influences gene body methylation of Wnt signaling-related genes in hiPSCs. These findings suggest that SALL3 switches the differentiation propensity of hiPSCs toward distinct cell lineages by changing the epigenetic profile and serves as a marker for evaluating the hiPSC differentiation propensity.
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spelling pubmed-65203852019-05-20 SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation Kuroda, Takuya Yasuda, Satoshi Tachi, Shiori Matsuyama, Satoko Kusakawa, Shinji Tano, Keiko Miura, Takumi Matsuyama, Akifumi Sato, Yoji Nat Commun Article Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlates positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. Without affecting self-renewal of hiPSCs, SALL3 knockdown inhibits ectoderm differentiation and conversely enhances mesodermal/endodermal differentiation. Similarly, loss- and gain-of-function studies reveal that SALL3 inversely regulates the differentiation of hiPSCs into cardiomyocytes and neural cells. Mechanistically, SALL3 modulates DNMT3B function and DNA methyltransferase activity, and influences gene body methylation of Wnt signaling-related genes in hiPSCs. These findings suggest that SALL3 switches the differentiation propensity of hiPSCs toward distinct cell lineages by changing the epigenetic profile and serves as a marker for evaluating the hiPSC differentiation propensity. Nature Publishing Group UK 2019-05-15 /pmc/articles/PMC6520385/ /pubmed/31092818 http://dx.doi.org/10.1038/s41467-019-09511-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kuroda, Takuya
Yasuda, Satoshi
Tachi, Shiori
Matsuyama, Satoko
Kusakawa, Shinji
Tano, Keiko
Miura, Takumi
Matsuyama, Akifumi
Sato, Yoji
SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
title SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
title_full SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
title_fullStr SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
title_full_unstemmed SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
title_short SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
title_sort sall3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520385/
https://www.ncbi.nlm.nih.gov/pubmed/31092818
http://dx.doi.org/10.1038/s41467-019-09511-4
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