Chirality controls mesenchymal stem cell lineage diversification through mechanoresponses

Yan Wei, Shengjie Jiang, Mengting Si, Xuehui Zhang, Jinying Liu, Zheng Wang, Cen Cao, Jianyong Huang, Houbing Huang, Lili Chen, Shutao Wang, Chuanliang Feng, Xuliang Deng, Lei Jiang

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12 Citations (Scopus)

Abstract

Biogenesis and tissue development are based on the heterogenesis of multipotent stem cells. However, the underlying mechanisms of stem cell fate specification are unclear. Chirality is one of the most crucial factors that affects stem cell development and is implicated in asymmetrical cell morphology formation; however, its function in heterogeneous cell fate determination remains elusive. In this study, it is reported that the chirality of a constructed 3D extracellular matrix (ECM) differentiates mesenchymal stem cells to diverse lineages of osteogenic and adipogenic cells by providing primary heterogeneity. Molecular analysis shows that left-handed chirality of the ECM enhances the clustering of the mechanosensor Itgα5, while right-handed chirality decreases this effect. These differential adhesion patterns further activate distinct mechanotransduction events involving the contractile state, focal adhesion kinase/extracellular signal-regulated kinase 1/2 cascades, and yes-associated protein/runt-related transcription factor 2 nuclear translocation, which direct heterogeneous differentiation. Moreover, theoretical modeling demonstrates that diverse chirality mechanosensing is initiated by biphasic modes of fibronectin tethering. The findings of chirality-dependent lineage specification of stem cells provide potential strategies for the biogenesis of organisms and regenerative therapies.

Original languageEnglish
Article number1900582
Number of pages10
JournalAdvanced Materials
Volume31
Issue number16
DOIs
Publication statusPublished - 19 Apr 2019
Externally publishedYes

Keywords

  • cellular mechanics
  • lineage diversification
  • matrix chirality

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