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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.