Specialized Mechanosensory Epithelial Cells in Mouse Gut Intrinsic Tactile Sensitivity.
Enteroendocrine Cell
GI Physiology
Ion Channels
Mechanosensitivity
Neuroepithelial Connection
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
02
06
2021
revised:
30
08
2021
accepted:
12
10
2021
pubmed:
25
10
2021
medline:
23
2
2022
entrez:
24
10
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34688712
pii: S0016-5085(21)03664-7
doi: 10.1053/j.gastro.2021.10.026
pmc: PMC8792331
mid: NIHMS1761530
pii:
doi:
Substances chimiques
Ion Channels
0
Piezo2 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
535-547.e13Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK052766
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123549
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Organisme : NIDDK NIH HHS
ID : F99 DK123834
Pays : United States
Organisme : NCCIH NIH HHS
ID : DP2 AT010875
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS118790
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.
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