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Tracing the origin of adult intestinal stem cells
Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Letter › peer review
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986928/pdf/EMS85477.pdf
Indsendt manuskript
DOI
- https://doi.org/10.1038/s41586-019-1212-5
Forlagets udgivne version
- Jordi Guiu, Københavns Universitet ,
- Edouard Hannezo, Institute of Science and Technology Austria, Klosterneuburg, Austria. ,
- Shiro Yui, Tokyo Medical and Dental University ,
- Samuel Demharter, Københavns Universitet ,
- Svetlana Ulyanchenko, Københavns Universitet ,
- Martti Maimets, Københavns Universitet ,
- Anne Jørgensen, Københavns Universitet ,
- Signe Perlman, Københavns Universitet ,
- Lene Lundvall, Københavns Universitet ,
- Linn Salto Mamsen, Laboratory of Reproductive Biology, Section 5712, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, University of Copenhagen, Rigshospitalet, Copenhagen DK-2100, Denmark. ,
- Agnete Larsen
- Rasmus H Olesen ,
- Claus Yding Andersen, Laboratory of Reproductive Biology, Section 5712, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, University of Copenhagen, Rigshospitalet, Copenhagen DK-2100, Denmark. ,
- Lea Langhoff Thuesen, Københavns Universitet ,
- Kristine Juul Hare, Københavns Universitet ,
- Tune H Pers, Københavns Universitet ,
- Konstantin Khodosevich, Københavns Universitet ,
- Benjamin D Simons, University of Cambridge ,
- Kim B Jensen, Københavns Universitet
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature |
| Vol/bind | 570 |
| Nummer | 7759 |
| Sider (fra-til) | 107-111 |
| Antal sider | 5 |
| ISSN | 0028-0836 |
| DOI | |
| Status | Udgivet - jun. 2019 |
Se relationer på Aarhus Universitet Citationsformater
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