Tracing the origin of adult intestinal stem cells.
Mamsen, Linn Salto
Olesen, Rasmus H
Thuesen, Lea Langhoff
Hare, Kristine Juul
Nature Publishing Group
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Guiu, J., Hannezo, E., Yui, S., Demharter, S., Ulyanchenko, S., Maimets, M., Jørgensen, A., et al. (2019). Tracing the origin of adult intestinal stem cells.. Nature, 570 (7759), 107-111. https://doi.org/10.1038/s41586-019-1212-5
Adult Intestinal Stem Cells (ISCs) are located at the bottom of crypts of Lieberkuhn, where they express markers such as Lgr5, and fuel the constant replenishment of the intestinal epithelium. Although fetal Lgr5 expressing cells can give rise to adult ISCs, it remains unclear whether this population in the patterned epithelium represents unique ISC precursors. Using unbiased quantitative lineage-tracing approaches, biophysical modeling and intestinal transplantation, we show 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 ISC pool. Based on 3D imaging, we find that, during fetal development, villi undergo gross remodeling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, enabling them to contribute to the adult stem cell niche. Our results demonstrate that large-scale remodeling of the intestinal walland cell fate specification are intertwined processes. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage, revealing that stem cell identity is an induced rather than a hardwired property.
Intestines, Intestinal Mucosa, Stem Cells, Fetus, Animals, Mice, Receptors, G-Protein-Coupled, Regeneration, Cell Differentiation, Cell Lineage, Female, Male, Stem Cell Niche, Cellular Reprogramming
wellcome trust royal society
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
External DOI: https://doi.org/10.1038/s41586-019-1212-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291885
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