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Tracing the origin of adult intestinal stem cells.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Guiu, Jordi 
Hannezo, Edouard 
Yui, Shiro 
Demharter, Samuel 
Ulyanchenko, Svetlana 

Abstract

Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR51,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium-irrespective of their location and pattern of LGR5 expression in the fetal gut tube-contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5-9, revealing that stem-cell identity is an induced rather than a hardwired property.

Description

Keywords

Animals, Cell Differentiation, Cell Lineage, Cellular Reprogramming, Female, Fetus, Intestinal Mucosa, Intestines, Male, Mice, Receptors, G-Protein-Coupled, Regeneration, Stem Cell Niche, Stem Cells

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

570

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Medical Research Council (MC_PC_12009)
European Commission Horizon 2020 (H2020) Societal Challenges (668294-2 INTENS)
Wellcome Trust (110326/Z/15/Z)
wellcome trust royal society