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Selective laminin-directed differentiation of human induced pluripotent stem cells into distinct ocular lineages

Shibata, Shun, Hayashi, Ryuhei, Okubo, Toru, Kudo, Yuji, Katayama, Tomohiko, Ishikawa, Yuki, Toga, Junko, Yagi, Emiko, Honma, Yoichi, Quantock, Andrew J. ORCID:, Sekiguchi, Kiyotoshi and Nishida, Kohji 2018. Selective laminin-directed differentiation of human induced pluripotent stem cells into distinct ocular lineages. Cell Reports 25 (6) , pp. 1668-1679. 10.1016/j.celrep.2018.10.032

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Publisher: Elsevier
ISSN: 2211-1247
Funders: BBSRC
Date of First Compliant Deposit: 5 November 2020
Date of Acceptance: 5 October 2018
Last Modified: 04 May 2023 23:42

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