title: PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors.
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.
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schrenk-Siemens
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hagen
authors.initials: H
authors.lastname: Wende
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Prato
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rostock
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Loewer
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and University Medical Center Mannheim, Mannheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Gary R
authors.identifier: 0000000228906352
authors.initials: GR
authors.lastname: Lewin
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Lechner
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Siemens
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008465:Mechanoreceptors / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology; D009432:Neural Crest / Q000166:cytology; D011984:Sensory Receptor Cells / Q000502:physiology*; D014110:Touch / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C491183:NEUROG2 protein, human; C000589132:PIEZO2 protein, human; C552921:Piezo2 protein, mouse