4.8 Article

Nanotopography regulates motor neuron differentiation of human pluripotent stem cells

期刊

NANOSCALE
卷 10, 期 7, 页码 3556-3565

出版社

ROYAL SOC CHEMISTRY
DOI: 10.1039/c7nr05430k

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资金

  1. National Science Foundation [CMMI 1129611, CBET 1149401, CMMI 1536087]
  2. National Institute of Health [R01 DE016530]
  3. American Heart Association Scientist Development Grant [16SDG31020038]
  4. National Science Foundation
  5. NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE016530] Funding Source: NIH RePORTER

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The regulation of human pluripotent stem cell (hPSC) behaviors has been mainly studied through exploration of biochemical factors. However, the current directed differentiation protocols for hPSCs that completely rely on biochemical factors remain suboptimal. It has recently become evident that coexisting biophysical signals in the stem cell microenvironment, including nanotopographic cues, can provide potent regulatory signals to mediate adult stem cell behaviors, including self-renewal and differentiation. Herein, we utilized a recently developed, large-scale nanofabrication technique based on reactive-ion etching (RIE) to generate random nanoscale structures on glass surfaces with high precision and reproducibility. We report here that hPSCs are sensitive to nanotopographic cues and such nanotopographic sensitivity can be leveraged for improving directed neuronal differentiation of hPSCs. We demonstrate early neuroepithelial conversion and motor neuron (MN) progenitor differentiation of hPSCs can be promoted using nanoengineered topographic substrates. We further explore how hPSCs sense the substrate nanotopography and relay this biophysical signal through a regulatory signaling network involving cell adhesion, the actomyosin cytoskeleton, and Hippo/YAP signaling to mediate the neuroepithelial induction of hPSCs. Our study provides an efficient method for large-scale production of MNs from hPSCs, useful for regenerative medicine and cell-based therapies.

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