Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages

Summary: The extracellular matrix plays a key role in stem cell maintenance, expansion, and differentiation. Laminin, a basement membrane protein, is a widely used substrate for cell culture including the growth of human induced pluripotent stem cells (hiPSCs). Here, we show that different isoforms...

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Main Authors: Shun Shibata, Ryuhei Hayashi, Toru Okubo, Yuji Kudo, Tomohiko Katayama, Yuki Ishikawa, Junko Toga, Emiko Yagi, Yoichi Honma, Andrew J. Quantock, Kiyotoshi Sekiguchi, Kohji Nishida
Format: Article
Language:English
Published: Elsevier 2018-11-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718316085
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author Shun Shibata
Ryuhei Hayashi
Toru Okubo
Yuji Kudo
Tomohiko Katayama
Yuki Ishikawa
Junko Toga
Emiko Yagi
Yoichi Honma
Andrew J. Quantock
Kiyotoshi Sekiguchi
Kohji Nishida
author_facet Shun Shibata
Ryuhei Hayashi
Toru Okubo
Yuji Kudo
Tomohiko Katayama
Yuki Ishikawa
Junko Toga
Emiko Yagi
Yoichi Honma
Andrew J. Quantock
Kiyotoshi Sekiguchi
Kohji Nishida
author_sort Shun Shibata
collection DOAJ
description Summary: The extracellular matrix plays a key role in stem cell maintenance, expansion, and differentiation. Laminin, a basement membrane protein, is a widely used substrate for cell culture including the growth of human induced pluripotent stem cells (hiPSCs). Here, we show that different isoforms of laminin lead to the selective differentiation of hiPSCs into different eye-like tissues. Specifically, the 211 isoform of the E8 fragment of laminin (LN211E8) promotes differentiation into neural crest cells via Wnt activation, whereas LN332E8 promotes differentiation into corneal epithelial cells. The immunohistochemical distributions of these laminin isoforms in the developing mouse eye mirrors the hiPSC type that was induced in vitro. Moreover, LN511E8 enables generation of dense hiPSC colonies due to actomyosin contraction, which in turn led to cell density-dependent YAP inactivation and subsequent retinal differentiation in colony centers. Thus, distinct laminin isoforms determine the fate of expanded hiPSCs into eye-like tissues. : Shibata et al. report that laminin isoforms differentially regulate the ocular cell differentiation from hiPSCs. The binding affinity of laminin and integrins determines the nature of expanded hiPSC colonies in terms of cell motility, cell-cell interactions, and cell density, with the involvement of Wnt and YAP signals. Keywords: human induced pluripotent stem cells, hiPSCs, laminin isoforms, YAP, Wnt, ocular cell differentiation, self-formed ectodermal autonomous multi-zone, SEAM
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spelling doaj.art-cf53b36690bf48caa88fe3ccedb9f4cb2022-12-22T03:41:05ZengElsevierCell Reports2211-12472018-11-0125616681679.e5Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular LineagesShun Shibata0Ryuhei Hayashi1Toru Okubo2Yuji Kudo3Tomohiko Katayama4Yuki Ishikawa5Junko Toga6Emiko Yagi7Yoichi Honma8Andrew J. Quantock9Kiyotoshi Sekiguchi10Kohji Nishida11Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Research and Development Division, ROHTO Pharmaceutical Co., Ltd., Osaka, Osaka 544-8666, JapanDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Corresponding authorDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Research and Development Division, ROHTO Pharmaceutical Co., Ltd., Osaka, Osaka 544-8666, JapanDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Research and Development Division, ROHTO Pharmaceutical Co., Ltd., Osaka, Osaka 544-8666, JapanDepartment of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDepartment of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanDivision of Matrixome Research and Application, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, JapanDivision of Matrixome Research and Application, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Research and Development Division, ROHTO Pharmaceutical Co., Ltd., Osaka, Osaka 544-8666, JapanStructural Biophysics Group, School of Optometry and Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF24 4HQ, Wales, UKDivision of Matrixome Research and Application, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Corresponding authorSummary: The extracellular matrix plays a key role in stem cell maintenance, expansion, and differentiation. Laminin, a basement membrane protein, is a widely used substrate for cell culture including the growth of human induced pluripotent stem cells (hiPSCs). Here, we show that different isoforms of laminin lead to the selective differentiation of hiPSCs into different eye-like tissues. Specifically, the 211 isoform of the E8 fragment of laminin (LN211E8) promotes differentiation into neural crest cells via Wnt activation, whereas LN332E8 promotes differentiation into corneal epithelial cells. The immunohistochemical distributions of these laminin isoforms in the developing mouse eye mirrors the hiPSC type that was induced in vitro. Moreover, LN511E8 enables generation of dense hiPSC colonies due to actomyosin contraction, which in turn led to cell density-dependent YAP inactivation and subsequent retinal differentiation in colony centers. Thus, distinct laminin isoforms determine the fate of expanded hiPSCs into eye-like tissues. : Shibata et al. report that laminin isoforms differentially regulate the ocular cell differentiation from hiPSCs. The binding affinity of laminin and integrins determines the nature of expanded hiPSC colonies in terms of cell motility, cell-cell interactions, and cell density, with the involvement of Wnt and YAP signals. Keywords: human induced pluripotent stem cells, hiPSCs, laminin isoforms, YAP, Wnt, ocular cell differentiation, self-formed ectodermal autonomous multi-zone, SEAMhttp://www.sciencedirect.com/science/article/pii/S2211124718316085
spellingShingle Shun Shibata
Ryuhei Hayashi
Toru Okubo
Yuji Kudo
Tomohiko Katayama
Yuki Ishikawa
Junko Toga
Emiko Yagi
Yoichi Honma
Andrew J. Quantock
Kiyotoshi Sekiguchi
Kohji Nishida
Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
Cell Reports
title Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
title_full Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
title_fullStr Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
title_full_unstemmed Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
title_short Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
title_sort selective laminin directed differentiation of human induced pluripotent stem cells into distinct ocular lineages
url http://www.sciencedirect.com/science/article/pii/S2211124718316085
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