2. Academic Validation
  3. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells

Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells

  • Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16148-53. doi: 10.1073/pnas.1409802111.
Medha M Pathak 1,  Jamison L Nourse 2,  Truc Tran 3,  Jennifer Hwe 3,  Janahan Arulmoli 4,  Dai Trang T Le 3,  Elena Bernardis 5,  Lisa A Flanagan 6,  Francesco Tombola 1
Affiliations

Affiliations

  • 1 Departments of Physiology and Biophysics, medhap@uci.edu ftombola@uci.edu.
  • 2 Neurology, and Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697; and.
  • 3 Departments of Physiology and Biophysics.
  • 4 Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697; and Biomedical Engineering and.
  • 5 Section of Dermatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
  • 6 Neurology, and Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697; and Biomedical Engineering and.
PMID: 25349416 DOI: 10.1073/pnas.1409802111
Abstract

Neural stem cells are multipotent cells with the ability to differentiate into neurons, astrocytes, and oligodendrocytes. Lineage specification is strongly sensitive to the mechanical properties of the cellular environment. However, molecular pathways transducing matrix mechanical cues to intracellular signaling pathways linked to lineage specification remain unclear. We found that the mechanically gated ion channel Piezo1 is expressed by brain-derived human neural stem/progenitor cells and is responsible for a mechanically induced ionic current. Piezo1 activity triggered by traction forces elicited influx of CA(2+), a known modulator of differentiation, in a substrate-stiffness-dependent manner. Inhibition of channel activity by the pharmacological inhibitor GsMTx-4 or by siRNA-mediated Piezo1 knockdown suppressed neurogenesis and enhanced astrogenesis. Piezo1 knockdown also reduced the nuclear localization of the mechanoreactive transcriptional coactivator Yes-associated protein. We propose that the mechanically gated ion channel Piezo1 is an important determinant of mechanosensitive lineage choice in neural stem cells and may play similar roles in other multipotent stem cells.

Keywords

Yap/Taz; blebbistatin; calcium signaling; matrix mechanics; myosin II.

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