title: Pan-neuronal maturation but not neuronal subtype differentiation of adult neural stem cells is mechanosensitive.
abstract: Most past studies of the biophysical regulation of stem cell differentiation have focused on initial lineage commitment or proximal differentiation events. It would be valuable to understand whether biophysical inputs also influence distal endpoints more closely associated with physiological function, such as subtype specification in neuronal differentiation. To explore this question, we cultured adult neural stem cells (NSCs) on variable stiffness ECMs under conditions that promote neuronal fate commitment for extended time periods to allow neuronal subtype differentiation. We find that ECM stiffness does not modulate the expression of NeuroD1 and TrkA/B/C or the percentages of pan-neuronal, GABAergic, or glutamatergic neuronal subtypes. Interestingly, however, an ECM stiffness of 700 Pa maximizes expression of pan-neuronal markers. These results suggest that a wide range of stiffnesses fully permit pan-neuronal NSC differentiation, that an intermediate stiffness optimizes expression of pan-neuronal genes, and that stiffness does not impact commitment to particular neuronal subtypes.
authors: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
authors: Albert J
authors: AJ
authors: Keung
authors: Meimei
authors: M
authors: Dong
authors: David V
authors: DV
authors: Schaffer
authors: Sanjay
authors: S
authors: Kumar
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D060833:Cellular Microenvironment / Q000502:physiology; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014404:Tubulin / Q000235:genetics
chemical_list: D014404:Tubulin
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