The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Crypt Base Columnar Stem Cells in Small Intestines of Mice Are Radioresistant
Open accessAbstract
BACKGROUND & AIMS Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that they are highly radiosensitive. Cycling crypt base columnar cells (CBCs) at crypt positions +1–3 recently were defined as an alternative population of ISCs. Little is known about the sensitivity of this stem cell population to radiation. METHODS Radiation-induced lethality of CBCs was quantified kinetically in Lgr5-lacZ transgenic mice. γ-H2AX, BRCA1, RAD51, and DNA-PKcs foci were used as DNA repair surrogates to investigate the inherent ability of CBCs to recognize and repair double-strand breaks. 5-ethynyl-2′-deoxyuridine and 5-bromo-2′-deoxyuridine incorporation assays were used to study patterns of CBC growth arrest and re-initiation of cell cycling. Apoptosis was evaluated by caspase-3 staining. RESULTS CBCs are relatively radioresistant, repairing DNA by homologous recombination significantly more efficiently than transit amplifying progenitors or villus cells. CBCs undergo apoptosis less than 24 hours after irradiation (32% ± 2% of total lethality) or mitotic death at 24–48 hours. Survival of CBCs at 2 days predicts crypt regeneration at 3.5 days and lethality from gastrointestinal syndrome. Crypt repopulation originates from CBCs that survive irradiation. CONCLUSIONS Adult ISCs in mice can cycle rapidly yet still be radioresistant. Importantly, homologous recombination can protect adult stem cell populations from genotoxic stress. These findings broaden and refine concepts of the phenotype of adult stem cells.
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
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Self-citationIdentification of stem cells in small intestine and colon by marker gene Lgr5
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Self-citationThe DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368
Paneth 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
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Self-citationInterconversion Between Intestinal Stem Cell Populations in Distinct Niches
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Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis
Mohrin, M., Bourke, E., Alexander, D., Warr, M. R., Barry-Holson, K., Le Beau, M. M., Morrison, C. G., & Passegué, E. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.06.014 · Cited by 599
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Assembly and function of DNA double-strand break repair foci in mammalian cells
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Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796
Lgr5 stem cells are indispensable for radiation-induced intestinal regeneration
Metcalfe, C., Kljavin, N. M., Ybarra, R., & de Sauvage, F. J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2013.11.008 · Cited by 575
Radiation enteropathy—pathogenesis, treatment and prevention
Hauer-Jensen, M., Denham, J. W., & Andreyev, H. J. N. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2014.46 · Cited by 489
Vitale, I., Manic, G., De Maria, R., Kroemer, G., & Galluzzi, L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.006 · Cited by 361
Qi, Z., Li, Y., Zhao, B., Xu, C., Liu, Y., Li, H., Zhang, B., Wang, X., Yang, X., Xie, W., et al. (2017) · Nature Communications · doi:10.1038/ncomms13824 · Cited by 320
Metadata
- Authors
- Hua, G., Thin, T. H., Feldman, R., Haimovitz–Friedman, A., Clevers, H., Fuks, Z., & Kolesnick, R.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 143
- Issue
- 5
- Pages
- 1266-1276
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2131815586
- Cited by
- 207
- References
- 9
- FWCI
- 12.02
- Type
- journal article
- Language
- en
- Open access
- green
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