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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-6520385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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