Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2
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Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2. / Zhu, Shuyong; Stanslowsky, Nancy; Fernández-Trillo, Jorge; Mamo, Tamrat M; Yu, Pengfei; Kalmbach, Norman; Ritter, Birgit; Eggenschwiler, Reto; Ouwendijk, Werner J D; Mzinza, David; Tan, Likai; Leffler, Andreas; Spohn, Michael; Brown, Richard J P; Kropp, Kai A; Kaever, Volkhard; Ha, Teng-Cheong; Narayanan, Pratibha; Grundhoff, Adam; Förster, Reinhold; Schambach, Axel; Verjans, Georges M G M; Schmidt, Manuela; Kispert, Andreas; Cantz, Tobias; Gomis, Ana; Wegner, Florian; Viejo-Borbolla, Abel.
in: STEM CELL RES, Jahrgang 56, 102535, 10.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2
AU - Zhu, Shuyong
AU - Stanslowsky, Nancy
AU - Fernández-Trillo, Jorge
AU - Mamo, Tamrat M
AU - Yu, Pengfei
AU - Kalmbach, Norman
AU - Ritter, Birgit
AU - Eggenschwiler, Reto
AU - Ouwendijk, Werner J D
AU - Mzinza, David
AU - Tan, Likai
AU - Leffler, Andreas
AU - Spohn, Michael
AU - Brown, Richard J P
AU - Kropp, Kai A
AU - Kaever, Volkhard
AU - Ha, Teng-Cheong
AU - Narayanan, Pratibha
AU - Grundhoff, Adam
AU - Förster, Reinhold
AU - Schambach, Axel
AU - Verjans, Georges M G M
AU - Schmidt, Manuela
AU - Kispert, Andreas
AU - Cantz, Tobias
AU - Gomis, Ana
AU - Wegner, Florian
AU - Viejo-Borbolla, Abel
N1 - Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2021/10
Y1 - 2021/10
N2 - Somatosensory low threshold mechanoreceptors (LTMRs) sense innocuous mechanical forces, largely through specialized axon termini termed sensory nerve endings, where the mechanotransduction process initiates upon activation of mechanotransducers. In humans, a subset of sensory nerve endings is enlarged, forming bulb-like expansions, termed bulbous nerve endings. There is no in vitro human model to study these neuronal endings. Piezo2 is the main mechanotransducer found in LTMRs. Recent evidence shows that Piezo1, the other mechanotransducer considered absent in dorsal root ganglia (DRG), is expressed at low level in somatosensory neurons. We established a differentiation protocol to generate, from iPSC-derived neuronal precursor cells, human LTMR recapitulating bulbous sensory nerve endings and heterogeneous expression of Piezo1 and Piezo2. The derived neurons express LTMR-specific genes, convert mechanical stimuli into electrical signals and have specialized axon termini that morphologically resemble bulbous nerve endings. Piezo2 is concentrated within these enlarged axon termini. Some derived neurons express low level Piezo1, and a subset co-express both channels. Thus, we generated a unique, iPSCs-derived human model that can be used to investigate the physiology of bulbous sensory nerve endings, and the role of Piezo1 and 2 during mechanosensation.
AB - Somatosensory low threshold mechanoreceptors (LTMRs) sense innocuous mechanical forces, largely through specialized axon termini termed sensory nerve endings, where the mechanotransduction process initiates upon activation of mechanotransducers. In humans, a subset of sensory nerve endings is enlarged, forming bulb-like expansions, termed bulbous nerve endings. There is no in vitro human model to study these neuronal endings. Piezo2 is the main mechanotransducer found in LTMRs. Recent evidence shows that Piezo1, the other mechanotransducer considered absent in dorsal root ganglia (DRG), is expressed at low level in somatosensory neurons. We established a differentiation protocol to generate, from iPSC-derived neuronal precursor cells, human LTMR recapitulating bulbous sensory nerve endings and heterogeneous expression of Piezo1 and Piezo2. The derived neurons express LTMR-specific genes, convert mechanical stimuli into electrical signals and have specialized axon termini that morphologically resemble bulbous nerve endings. Piezo2 is concentrated within these enlarged axon termini. Some derived neurons express low level Piezo1, and a subset co-express both channels. Thus, we generated a unique, iPSCs-derived human model that can be used to investigate the physiology of bulbous sensory nerve endings, and the role of Piezo1 and 2 during mechanosensation.
KW - Humans
KW - Induced Pluripotent Stem Cells/metabolism
KW - Ion Channels/genetics
KW - Mechanoreceptors/metabolism
KW - Mechanotransduction, Cellular
KW - Nerve Endings/metabolism
KW - Sensory Receptor Cells/metabolism
U2 - 10.1016/j.scr.2021.102535
DO - 10.1016/j.scr.2021.102535
M3 - SCORING: Journal article
C2 - 34607262
VL - 56
JO - STEM CELL RES
JF - STEM CELL RES
SN - 1873-5061
M1 - 102535
ER -