RRC ID |
54718
|
著者 |
Shibata S, Hayashi R, Okubo T, Kudo Y, Katayama T, Ishikawa Y, Toga J, Yagi E, Honma Y, Quantock AJ, Sekiguchi K, Nishida K.
|
タイトル |
Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages.
|
ジャーナル |
Cell Rep
|
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.
|
巻・号 |
25(6)
|
ページ |
1668-1679.e5
|
公開日 |
2018-11-6
|
DOI |
10.1016/j.celrep.2018.10.032
|
PII |
S2211-1247(18)31608-5
|
PMID |
30404017
|
MeSH |
Actomyosin / metabolism
Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Count
Cell Differentiation*
Cell Line
Cell Lineage*
Epithelium, Corneal / cytology
Eye / cytology*
Female
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Laminin / metabolism*
Mice, Inbred C57BL
Neural Crest / cytology
Pregnancy
Protein Isoforms / metabolism
Transcription Factors / metabolism
Wnt Proteins / metabolism
YAP-Signaling Proteins
|
IF |
7.815
|
引用数 |
7
|
リソース情報 |
ヒト・動物細胞 |
201B7(HPS0063)
1383D2(HPS1005) |