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PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors

Official URL:https://doi.org/10.1038/nn.3894
PubMed:View item in PubMed
Creators Name:Schrenk-Siemens, K. and Wende, H. and Prato, V. and Song, K. and Rostock, C. and Loewer, A. and Utikal, J. and Lewin, G.R. and Lechner, S.G. and Siemens, J.
Journal Title:Nature Neuroscience
Journal Abbreviation:Nat Neurosci
Page Range:10-16
Date:January 2015
Keywords:Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cellular Mechanotransduction, Inbred C57BL Mice, Induced Pluripotent Stem Cells, Ion Channels, Knockout Mice, Mechanoreceptors, Nerve Tissue Proteins, Neural Crest, Sensory Receptor Cells, Touch, Animals, Mice
Abstract:Human sensory neurons are inaccessible for functional examination, and thus little is known about the mechanisms mediating touch sensation in humans. Here we demonstrate that the mechanosensitivity of human embryonic stem (hES) cell-derived touch receptors depends on PIEZO2. To recapitulate sensory neuron development in vitro, we established a multistep differentiation protocol and generated sensory neurons via the intermediate production of neural crest cells derived from hES cells or human induced pluripotent stem (hiPS) cells. The generated neurons express a distinct set of touch receptor-specific genes and convert mechanical stimuli into electrical signals, their most salient characteristic in vivo. Strikingly, mechanosensitivity is lost after CRISPR/Cas9-mediated PIEZO2 gene deletion. Our work establishes a model system that resembles human touch receptors, which may facilitate mechanistic analysis of other sensory subtypes and provide insight into developmental programs underlying sensory neuron diversity.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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