Title
Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages
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
Institution
Osaka University Graduate School of Medicine
Country
Japan
Year
2018
Journal
Cell Reports
Abstract
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.
Product use
Differentiation of iPSC into corneal limbal epithelial cells
Tissue type
Other
Tissue info
hiPSC lines 201B7 and 1383D2
Species
Human

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