Retrograde Movements Determine Effective Stem Cell Numbers in the Intestine

Overview

Journal Nature

Specialty Science

Date 2022 Jul 13

PMID 35831497

Authors

Maria Azkanaz

Bernat Corominas-Murtra

Saskia I J Ellenbroek

Lotte Bruens

Anna T Webb

Dimitrios Laskaris

Koen C Oost

Simona J A Lafirenze

Karl Annusver

Hendrik A Messal

Sharif Iqbal

Dustin J Flanagan

David J Huels

Felipe Rojas-Rodriguez

Miguel Vizoso

Maria Kasper

Owen J Sansom

Hugo J Snippert

Prisca Liberali

Benjamin D Simons

Pekka Katajisto

Edouard Hannezo

Jacco van Rheenen

Affiliations

Soon will be listed here.

Abstract

The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts. Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated.

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