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

Stem Cell Research

Nancy Stanslowsky¹  Jorge Fernández-Trillo²  Likai Tan³  Ana Gomis⁴  Andreas Kispert⁵  Manuela Schmidt⁶  Kai A. Kropp⁷  Reto Eggenschwiler⁸  Tamrat M. Mamo⁸  Andreas Leffler⁹  Florian Wegner⁹  Teng-Cheong Ha^1,10  Tobias Cantz^1,11  Reinhold Förster^1,11  Richard J.P. Brown^1,12  Michael Spohn^1,12  Norman Kalmbach^1,13  Birgit Ritter^1,14  Werner J.D. Ouwendijk^1,14  Shuyong Zhu^1,14  Pratibha Narayanan^1,14  Pengfei Yu^1,15  Abel Viejo-Borbolla^1,16  Axel Schambach^1,16  Adam Grundhoff^1,17  David Mzinza^1,18  Georges M.G.M. Verjans^1,19  Volkhard Kaever^1,19 

[1] Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Germany;Corresponding authors at: Institute of Virology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.;Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany;Division of Hematology/Oncology, Boston Children’s Hospital, Harvard Medical School, MA, USA;Institute of Immunology, Hannover Medical School, Germany;Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Germany;Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Germany;Department of Neurology, Hannover Medical School, Germany;Department of Viroscience, Erasmus Medical Center, the Netherlands;Division of Veterinary Medicine, Paul-Ehrlich-Institute, Germany;Institute of Experimental Hematology, Hannover Medical School, Germany;Institute of Immunology, Hannover Medical School, Germany;Institute of Molecular Biology, Hannover Medical School, Germany;Institute of Virology, Hannover Medical School, Germany;Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Spain;Max Planck Institute of Experimental Medicine, Germany;Research Core Unit Metabolomics, Institute of Pharmacology, Hannover Medical School, Germany;Research Group Translational Hepatology and Stem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, Germany;The Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Germany;

关键词: Human induced pluripotent stem cells;    Small molecule-derived neural precursor cells;    Low threshold mechanoreceptors;    Bulbous sensory nerve ending;    Piezo1, Piezo2;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown