Control of matrix stiffness promotes endodermal lineage specification by regulating SMAD2/3 via lncRNA LINC00458
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AbstractDuring endoderm formation, cell identity and tissue morphogenesis are tightly controlled by cell-intrinsic and cell-extrinsic factors such as biochemical and physical inputs. While the effects of biochemical factors are well studied, the physical cues that regulate cell division and differentiation are poorly understood. RNA sequencing analysis demonstrated increases of endoderm-specific gene expression in hPSCs cultured on soft substrate (Young’s modulus, 3 ± 0.45 kPa) in comparison with hard substrate (Young’s modulus, 165 ± 6.39 kPa). Further analyses revealed that multiple long noncoding RNAs (lncRNAs) were up-regulated on soft substrate; among them, LINC00458 was identified as a stiffness-dependent lncRNA specifically required for hPSC differentiation toward an early endodermal lineage. Gain- and loss-of-function experiments confirmed that LINC00458 is functionally required for hPSC endodermal lineage specification induced by soft substrates. Our study provides evidence that mechanical cues regulate the expression of LINC00458 and induce differentiation of hPSC into hepatic lineage progenitors.
All Author(s) ListChen YF, Li YSJ, Chou CH, Chiew MY, Huang HD, Ho JHC, Chien S, Lee OK
Journal nameScience Advances
Volume Number6
Issue Number6
Article numbereaay0264
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesMultidisciplinary Sciences;Science & Technology - Other Topics

Last updated on 2020-24-05 at 23:36