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Defining the contribution of Troy-positive progenitor cells to the mouse esophageal epithelium

Grommisch, David ; Wang, Menghan ; Eenjes, Evelien ; Svetličič, Maja ; Deng, Qiaolin ; Giselsson, Pontus LU orcid and Genander, Maria (2024) In Developmental Cell 59(10). p.6-1283
Abstract

Progenitor cells adapt their behavior in response to tissue demands. However, the molecular mechanisms controlling esophageal progenitor decisions remain largely unknown. Here, we demonstrate the presence of a Troy (Tnfrsf19)-expressing progenitor subpopulation localized to defined regions along the mouse esophageal axis. Lineage tracing and mathematical modeling demonstrate that Troy-positive progenitor cells are prone to undergoing symmetrical fate choices and contribute to esophageal tissue homeostasis long term. Functionally, TROY inhibits progenitor proliferation and enables commitment to differentiation without affecting fate symmetry. Whereas Troy expression is stable during esophageal homeostasis, progenitor cells downregulate... (More)

Progenitor cells adapt their behavior in response to tissue demands. However, the molecular mechanisms controlling esophageal progenitor decisions remain largely unknown. Here, we demonstrate the presence of a Troy (Tnfrsf19)-expressing progenitor subpopulation localized to defined regions along the mouse esophageal axis. Lineage tracing and mathematical modeling demonstrate that Troy-positive progenitor cells are prone to undergoing symmetrical fate choices and contribute to esophageal tissue homeostasis long term. Functionally, TROY inhibits progenitor proliferation and enables commitment to differentiation without affecting fate symmetry. Whereas Troy expression is stable during esophageal homeostasis, progenitor cells downregulate Troy in response to tissue stress, enabling proliferative expansion of basal cells refractory to differentiation and reestablishment of tissue homeostasis. Our results demonstrate functional, spatially restricted progenitor heterogeneity in the esophageal epithelium and identify how dynamic regulation of Troy coordinates tissue generation.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
differentiation, esophagus, fate choice, progenitor cell, proliferation, regeneration, Troy
in
Developmental Cell
volume
59
issue
10
pages
6 - 1283
publisher
Cell Press
external identifiers
  • scopus:85192731621
  • pmid:38565145
ISSN
1534-5807
DOI
10.1016/j.devcel.2024.03.011
language
English
LU publication?
yes
id
a7acd792-5c2b-4019-9708-96653f412047
date added to LUP
2024-05-27 15:42:33
date last changed
2024-06-10 16:38:19
@article{a7acd792-5c2b-4019-9708-96653f412047,
  abstract     = {{<p>Progenitor cells adapt their behavior in response to tissue demands. However, the molecular mechanisms controlling esophageal progenitor decisions remain largely unknown. Here, we demonstrate the presence of a Troy (Tnfrsf19)-expressing progenitor subpopulation localized to defined regions along the mouse esophageal axis. Lineage tracing and mathematical modeling demonstrate that Troy-positive progenitor cells are prone to undergoing symmetrical fate choices and contribute to esophageal tissue homeostasis long term. Functionally, TROY inhibits progenitor proliferation and enables commitment to differentiation without affecting fate symmetry. Whereas Troy expression is stable during esophageal homeostasis, progenitor cells downregulate Troy in response to tissue stress, enabling proliferative expansion of basal cells refractory to differentiation and reestablishment of tissue homeostasis. Our results demonstrate functional, spatially restricted progenitor heterogeneity in the esophageal epithelium and identify how dynamic regulation of Troy coordinates tissue generation.</p>}},
  author       = {{Grommisch, David and Wang, Menghan and Eenjes, Evelien and Svetličič, Maja and Deng, Qiaolin and Giselsson, Pontus and Genander, Maria}},
  issn         = {{1534-5807}},
  keywords     = {{differentiation; esophagus; fate choice; progenitor cell; proliferation; regeneration; Troy}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{6--1283}},
  publisher    = {{Cell Press}},
  series       = {{Developmental Cell}},
  title        = {{Defining the contribution of Troy-positive progenitor cells to the mouse esophageal epithelium}},
  url          = {{http://dx.doi.org/10.1016/j.devcel.2024.03.011}},
  doi          = {{10.1016/j.devcel.2024.03.011}},
  volume       = {{59}},
  year         = {{2024}},
}