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

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…

• NS
  National Science Foundation

  Awards: IOS-1254060, 1254060, CAREER
• HH
  Helen Hay Whitney Foundation
• NI
  National Institutes of Health

  Awards: CA-62203, GM098973, UL1 TR000153, TR000153
• UO
  University of California, Irvine

  Awards: CA-62203, UL1 TR000153
• NC
  National Center for Research Resources

  Awards: TR000153, UL1 TR000153
• NC
  National Center for Advancing Translational Sciences

  Award: UL1 TR000153