@article{b5d21e735b254e7ea52e4ff1888a056e,
title = "Specialized Mechanosensory Epithelial Cells in Mouse Gut Intrinsic Tactile Sensitivity",
abstract = "Background and Aims: The gastrointestinal (GI) tract extracts nutrients from ingested meals while protecting the organism from infectious agents frequently present in meals. Consequently, most animals conduct the entire digestive process within the GI tract while keeping the luminal contents entirely outside the body, separated by the tightly sealed GI epithelium. Therefore, like the skin and oral cavity, the GI tract must sense the chemical and physical properties of the its external interface to optimize its function. Specialized sensory enteroendocrine cells (EECs) in GI epithelium interact intimately with luminal contents. A subpopulation of EECs express the mechanically gated ion channel Piezo2 and are developmentally and functionally like the skin's touch sensor— the Merkel cell. We hypothesized that Piezo2+ EECs endow the gut with intrinsic tactile sensitivity. Methods: We generated transgenic mouse models with optogenetic activators in EECs and Piezo2 conditional knockouts. We used a range of reference standard and novel techniques from single cells to living animals, including single-cell RNA sequencing and opto-electrophysiology, opto-organ baths with luminal shear forces, and in vivo studies that assayed GI transit while manipulating the physical properties of luminal contents. Results: Piezo2+ EECs have transcriptomic features of synaptically connected, mechanosensory epithelial cells. EEC activation by optogenetics and forces led to Piezo2-dependent alterations in colonic propagating contractions driven by intrinsic circuitry, with Piezo2+ EECs detecting the small luminal forces and physical properties of the luminal contents to regulate transit times in the small and large bowel. Conclusions: The GI tract has intrinsic tactile sensitivity that depends on Piezo2+ EECs and allows it to detect luminal forces and physical properties of luminal contents to modulate physiology.",
keywords = "Enteroendocrine Cell, GI Physiology, Ion Channels, Mechanosensitivity, Neuroepithelial Connection",
author = "Treichel, {Anthony J.} and Isabelle Finholm and Knutson, {Kaitlyn R.} and Constanza Alcaino and Whiteman, {Sara T.} and Brown, {Matthew R.} and Aleksey Matveyenko and Andrew Wegner and Halil Kacmaz and Arnaldo Mercado-Perez and Gajdos, {Gabriella Bedekovicsne} and Tamas Ordog and Madhusudan Grover and Joseph Szurszewski and Linden, {David R.} and Gianrico Farrugia and Arthur Beyder",
note = "Funding Information: The authors thank Peter Strege for help with the graphics; Gary Stoltz, Denika Kerska, and Tiffany Cassmann for technical assistance; Bob Highet for engineering; Simon J. Gibbons for constructive feedback; Lyndsay Busby for administrative assistance; and Michael Zumchak (Easy Learning Labs) for Excel guidance. Anthony J. Treichel and Isabelle Finholm contributed equally to this work. Anthony Treichel, BS (Data curation: Equal). Isabelle Finholm, BS (Data curation: Equal; Writing – original draft: Lead; Writing – review & editing: Lead). Kaitlyn Knutson, BS (Data curation: Supporting). Alcaino Constanza, PhD (Data curation: Supporting). Sara Whiteman, BS (Data curation: Supporting). Matthew Brown, BS (Data curation: Supporting). Aleksey Matveyenko, PhD (Data curation: Supporting). Andrew Wegner, BS (Data curation: Supporting). Halil Kacmaz, MD (Data curation: Supporting). Arnaldo Mercado-Perez, BS (Data curation: Supporting). Gabriella B. Gajdos, MS (Data curation: Supporting), Tamas Ordog, MD (Data curation: Supporting). Madhusudan Grover, MBBS (Data curation: Supporting). Joseph Szurszewski, PhD (Data curation: Supporting). David Linden, PhD (Data curation: Supporting). Gianrico Farrugia, MD (Data curation: Supporting). Arthur Beyder, MD, PhD (Data curation: Supporting; Writing – review & editing:, Equal). Funding This work was supported by the Mayo Clinic Department of Medicine K2R Award, National Institutes of Health grants DK123549, AT010875, NS118790 (Arthur Beyder), and DK052766 (Gianrico Farrugia, Arthur Beyder), and Mayo Clinic Center For Signaling in Gastroenterology (NIDDK P30DK084567). Funding Information: Funding This work was supported by the Mayo Clinic Department of Medicine K2R Award, National Institutes of Health grants DK123549, AT010875, NS118790 (Arthur Beyder), and DK052766 (Gianrico Farrugia, Arthur Beyder), and Mayo Clinic Center For Signaling in Gastroenterology (NIDDK P30DK084567). Publisher Copyright: {\textcopyright} 2022 AGA Institute",
year = "2022",
month = feb,
doi = "10.1053/j.gastro.2021.10.026",
language = "English (US)",
volume = "162",
pages = "535--547.e13",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "2",
}