ArticleProceedings of the National Academy of Sciences of the United States of America2023
Mechanosensitive stem cell fate choice is instructed by dynamic fluctuations in activation of Rho GTPases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- TiFM2.0 - versatile mechanical measurement and actuation in live embryos.Development (Cambridge, England) · 2026Article
- Tentonin 3 regulates the proliferation and migration of neural stem cells during embryonic brain development.BMC biology · 2026Article
- The Synthetic Extracellular Matrix as a Maestro of the In Vitro Stem Cell Niche: Orchestrating Fate and Function.Biomedicines · 2026Review
- Neuromechanobiology: Bridging Mechanobiology and Neuroscience Through Evidence and Open Questions.Cells · 2026Review
- Effects and mechanisms of iron overload on the proliferation and differentiation of preosteoblastic cellsFrontiers in bioengineering and biotechnology · 2026Article
- Effects of PDMS culture on stem cell differentiation towards definitive endoderm and hepatocytes.Acta biomaterialia · 2025Article
- Coordination of Focal Adhesion Nanoarchitecture and Dynamics in Mechanosensing for Cardiomyoblast Differentiation.ACS applied materials & interfaces · 2025Article
- Role of Neural Circuits in Cognitive Impairment.Neurochemical research · 2024Review
- Primate amnion development.Development (Cambridge, England) · 2024Review
- An explainable map of human gastruloid morphospace reveals gastrulation failure modes and predicts teratogens.bioRxiv : the preprint server for biology · 2024Article
- Spectrin mediates 3D-specific matrix stress-relaxation response in neural stem cell lineage commitment.Science advances · 2024Article
- Substrate stress relaxation regulates neural stem cell fate commitment.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Design of neural organoids engineered by mechanical forces.IBRO neuroscience reports · 2024Review
- Shining Light in Mechanobiology: Optical Tweezers, Scissors, and Beyond.ACS photonics · 2024Review
- Mapping morphogenesis and mechanics in embryo models.Nature methods · 2023Article
- Direct investigation of cell contraction signal networks by light-based perturbation methods.Pflugers Archiv : European journal of physiology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
During the intricate process by which cells give rise to tissues, embryonic and adult stem cells are exposed to diverse mechanical signals from the extracellular matrix (ECM) that influence their fate. Cells can sense these cues in part through dynamic generation of protrusions, modulated and controlled by cyclic activation of Rho GTPases. However, it remains unclear how extracellular mechanical signals regulate Rho GTPase activation dynamics and how such rapid, transient activation dynamics are integrated to yield long-term, irreversible cell fate decisions. Here, we report that ECM stiffness cues alter not only the magnitude but also the temporal frequency of RhoA and Cdc42 activation in adult neural stem cells (NSCs). Using optogenetics to control the frequency of RhoA and Cdc42 activation, we further demonstrate that these dynamics are functionally significant, where high- vs. low-frequency activation of RhoA and Cdc42 drives astrocytic vs. neuronal differentiation, respectively. In addition, high-frequency Rho GTPase activation induces sustained phosphorylation of the TGFβ pathway effector SMAD1, which in turn drives the astrocytic differentiation. By contrast, under low-frequency Rho GTPase stimulation, cells fail to accumulate SMAD1 phosphorylation and instead undergo neurogenesis. Our findings reveal the temporal patterning of Rho GTPase signaling and the resulting accumulation of an SMAD1 signal as a critical mechanism through which ECM stiffness cues regulate NSC fate.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.