Tracing the origin of adult intestinal stem cells

Jordi Guiu, Edouard Hannezo, Shiro Yui, Samuel Demharter, Svetlana Ulyanchenko, Martti Maimets, Anne Jørgensen, Signe Perlman, Lene Lundvall, Linn Salto Mamsen, Agnete Larsen, Rasmus H. Olesen, Claus Yding Andersen, Lea Langhoff Thuesen, Kristine Juul Hare, Tune H. Pers, Konstantin Khodosevich, Benjamin D. Simons and Kim B. Jensen ()
Additional contact information
Jordi Guiu: University of Copenhagen
Edouard Hannezo: University of Cambridge
Shiro Yui: University of Copenhagen
Samuel Demharter: University of Copenhagen
Svetlana Ulyanchenko: University of Copenhagen
Martti Maimets: University of Copenhagen
Anne Jørgensen: University of Copenhagen
Signe Perlman: University of Copenhagen
Lene Lundvall: University of Copenhagen
Linn Salto Mamsen: University Hospital of Copenhagen, University of Copenhagen
Agnete Larsen: Aarhus University
Rasmus H. Olesen: Aarhus University
Claus Yding Andersen: University Hospital of Copenhagen, University of Copenhagen
Lea Langhoff Thuesen: Hvidovre University Hospital
Kristine Juul Hare: Hvidovre University Hospital
Tune H. Pers: University of Copenhagen
Konstantin Khodosevich: University of Copenhagen
Benjamin D. Simons: University of Cambridge
Kim B. Jensen: University of Copenhagen

Nature, 2019, vol. 570, issue 7759, 107-111

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1212-5

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