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Dynamic light-responsive RhoA activity regulates mechanosensitive stem cell fate decision in 3D matrices
- Title
- Dynamic light-responsive RhoA activity regulates mechanosensitive stem cell fate decision in 3D matrices
- Authors
- Jieung; Kumar; Sanjay; Schaffer; David V.; Baek
- Ewha Authors
- 백지응
- Issue Date
- 2024
- Journal Title
- Biomaterials Advances
- ISSN
- 2772-9508
- Citation
- Biomaterials Advances vol. 160
- Keywords
- Early growth response (Egr1); Mechanosensing; Neural stem cell (NSC); Optogenetics; Ras homolog family member A (RhoA) signaling
- Publisher
- Elsevier Ltd
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- The behavior of stem cells is regulated by mechanical cues in their niche that continuously vary due to extracellular matrix (ECM) remodeling, pulsated mechanical stress exerted by blood flow, and/or cell migration. However, it is still unclear how dynamics of mechanical cues influence stem cell lineage commitment, especially in a 3D microenvironment where mechanosensing differs from that in a 2D microenvironment. In the present study, we investigated how temporally varying mechanical signaling regulates expression of the early growth response 1 gene (Egr1), which we recently discovered to be a 3D matrix-specific mediator of mechanosensitive neural stem cell (NSC) lineage commitment. Specifically, we temporally controlled the activity of Ras homolog family member A (RhoA), which is known to have a central role in mechanotransduction, using our previously developed Arabidopsis thaliana cryptochrome-2-based optoactivation system. Interestingly, pulsed RhoA activation induced Egr1 upregulation in stiff 3D gels only, whereas static light stimulation induced an increase in Egr1 expression across a wide range of 3D gel stiffnesses. Actin assembly inhibition limited Egr1 upregulation upon RhoA activation, implying that RhoA signaling requires an actin-involved process to upregulate Egr1. Consistently, static-light RhoA activation rather than pulsed-light activation restricted neurogenesis in soft gels. Our findings indicate that the dynamics of RhoA activation influence Egr1-mediated stem cell fate within 3D matrices in a matrix stiffness-dependent manner. © 2024
- DOI
- 10.1016/j.bioadv.2024.213836
- Appears in Collections:
- ETC > ETC
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