Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2

Shuyong Zhu; Nancy Stanslowsky; Jorge Fernández-Trillo; Tamrat M Mamo; Pengfei Yu; Norman Kalmbach; Birgit Ritter; Reto Eggenschwiler; Werner J D Ouwendijk; David Mzinza; Likai Tan; Andreas Leffler; Michael Spohn; Richard J P Brown; Kai A Kropp; Volkhard Kaever; Teng-Cheong Ha; Pratibha Narayanan; Adam Grundhoff; Reinhold Förster; Axel Schambach; Georges M G M Verjans; Manuela Schmidt; Andreas Kispert; Tobias Cantz; Ana Gomis; Florian Wegner; Abel Viejo-Borbolla

doi:10.1016/j.scr.2021.102535

Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2

Standard

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, Vol. 56, 102535, 10.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zhu, S, Stanslowsky, N, Fernández-Trillo, J, Mamo, TM, Yu, P, Kalmbach, N, Ritter, B, Eggenschwiler, R, Ouwendijk, WJD, Mzinza, D, Tan, L, Leffler, A, Spohn, M, Brown, RJP, Kropp, KA, Kaever, V, Ha, T-C, Narayanan, P, Grundhoff, A, Förster, R, Schambach, A, Verjans, GMGM, Schmidt, M, Kispert, A, Cantz, T, Gomis, A, Wegner, F & Viejo-Borbolla, A 2021, 'Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2', STEM CELL RES, vol. 56, 102535. https://doi.org/10.1016/j.scr.2021.102535

APA

Zhu, S., Stanslowsky, N., Fernández-Trillo, J., Mamo, T. M., Yu, P., Kalmbach, N., Ritter, B., Eggenschwiler, R., Ouwendijk, W. J. D., Mzinza, D., Tan, L., Leffler, A., Spohn, M., Brown, R. J. P., Kropp, K. A., Kaever, V., Ha, T-C., Narayanan, P., Grundhoff, A., ... Viejo-Borbolla, A. (2021). Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2. STEM CELL RES, 56, [102535]. https://doi.org/10.1016/j.scr.2021.102535

Vancouver

Zhu S, Stanslowsky N, Fernández-Trillo J, Mamo TM, Yu P, Kalmbach N et al. Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2. STEM CELL RES. 2021 Oct;56. 102535. https://doi.org/10.1016/j.scr.2021.102535

Bibtex

@article{8c5c278cd6ac4230b13b652ccff98541,

title = "Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2",

abstract = "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.",

keywords = "Humans, Induced Pluripotent Stem Cells/metabolism, Ion Channels/genetics, Mechanoreceptors/metabolism, Mechanotransduction, Cellular, Nerve Endings/metabolism, Sensory Receptor Cells/metabolism",

author = "Shuyong Zhu and Nancy Stanslowsky and Jorge Fern{\'a}ndez-Trillo and Mamo, {Tamrat M} and Pengfei Yu and Norman Kalmbach and Birgit Ritter and Reto Eggenschwiler and Ouwendijk, {Werner J D} and David Mzinza and Likai Tan and Andreas Leffler and Michael Spohn and Brown, {Richard J P} and Kropp, {Kai A} and Volkhard Kaever and Teng-Cheong Ha and Pratibha Narayanan and Adam Grundhoff and Reinhold F{\"o}rster and Axel Schambach and Verjans, {Georges M G M} and Manuela Schmidt and Andreas Kispert and Tobias Cantz and Ana Gomis and Florian Wegner and Abel Viejo-Borbolla",

year = "2021",

month = oct,

doi = "10.1016/j.scr.2021.102535",

language = "English",

volume = "56",

journal = "STEM CELL RES",

issn = "1873-5061",

publisher = "Elsevier",

}

RIS

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

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 -