The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging
Open accessAbstract
The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt. In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region. Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells. However, the short-term behaviour of individual Lgr5+ cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5-Confetti mice. We find that Lgr5+ cells in the upper part of the niche (termed ‘border cells’) can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed ‘central cells’, experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5+ cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.
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Cites
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Self-citationPaneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Intestinal label-retaining cells are secretory precursors expressing Lgr5
Buczacki, S. J. A., Zecchini, H. I., Nicholson, A. M., Russell, R., Vermeulen, L., Kemp, R., & Winton, D. J. (2013) · Nature · doi:10.1038/nature11965 · Cited by 761
Interconversion Between Intestinal Stem Cell Populations in Distinct Niches
Takeda, N., Jain, R., LeBoeuf, M. R., Wang, Q., Lu, M. M., & Epstein, J. A. (2011) · Science · doi:10.1126/science.1213214 · Cited by 742
Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells
Farin, H. F., Van Es, J. H., & Clevers, H. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.08.031 · Cited by 655
Self-citationStrategies for Homeostatic Stem Cell Self-Renewal in Adult Tissues
Simons, B. D., & Clevers, H. (2011) · Cell · doi:10.1016/j.cell.2011.05.033 · Cited by 489
Self-citationKozar, S., Morrissey, E., Nicholson, A. M., van der Heijden, M., Zecchini, H. I., Kemp, R., Tavaré, S., Vermeulen, L., & Winton, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.08.001 · Cited by 214
Cited by
Mesenchymal stem cell perspective: cell biology to clinical progress
Pittenger, M. F., Discher, D. E., Péault, B. M., Phinney, D. G., Hare, J. M., & Caplan, A. I. (2019) · npj Regenerative Medicine · doi:10.1038/s41536-019-0083-6 · Cited by 2,008
In Vitro Expansion of Human Gastric Epithelial Stem Cells and Their Responses to Bacterial Infection
Bartfeld, S., Bayram, T., van de Wetering, M., Huch, M., Begthel, H., Kujala, P., Vries, R., Peters, P. J., & Clevers, H. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.09.042 · Cited by 820
Self-citationAdult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later
Bond, A. M., Ming, G.-L., & Song, H. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.003 · Cited by 791
“…will also become possible to directly image the behavior of individual adult NSCs in vivo to explore how experience impacts NSC activation and division directly, as was achieved in adult fish (Barbosa et al., 2015) and for other adult somatic stem cells (Ritsma et al., 2014; Rompolas et al., 2012).”
BackgroundA distinct role for Lgr5+ stem cells in primary and metastatic colon cancer
de Sousa e Melo, F., Kurtova, A. V., Harnoss, J. M., Kljavin, N., Hoeck, J. D., Hung, J., Anderson, J. E., Storm, E. E., Modrusan, Z., Koeppen, H., et al. (2017) · Nature · doi:10.1038/nature21713 · Cited by 788
Self-citationPlasticity of epithelial stem cells in tissue regeneration
Blanpain, C., & Fuchs, E. (2014) · Science · doi:10.1126/science.1242281 · Cited by 589
Metadata
- Authors
- Ritsma, L., Ellenbroek, S. I. J., Zomer, A., Snippert, H. J., de Sauvage, F. J., Simons, B. D., Clevers, H., & van Rheenen, J.
- Venue
- Nature
- Published
- 2014-02-16
- Volume
- 507
- Issue
- 7492
- Pages
- 362-365
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2042423362
- Cited by
- 488
- References
- 7
- FWCI
- 29.01
- Type
- journal article
- Language
- en
- Open access
- green
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- Ritsma, L., Ellenbroek, S. I. J., Zomer, A., Snippert, H. J., de Sauvage, F. J., Simons, B. D., Clevers, H., & van Rheenen, J. (2014). Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature. https://doi.org/10.1038/nature12972
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