Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration

The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC...

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Bibliographic Details
Published in:	Cell stem cell Vol. 14; no. 2; p. 149
Main Authors:	Metcalfe, Ciara, Kljavin, Noelyn M, Ybarra, Ryan, de Sauvage, Frederic J
Format:	Journal Article
Language:	English
Published:	United States 06.02.2014
Subjects:	Adenomatous Polyposis Coli Protein - metabolism Animals Colitis - chemically induced Colitis - pathology Dextran Sulfate Diphtheria Toxin - pharmacology Dose-Response Relationship, Radiation Hyperplasia Intestines - drug effects Intestines - physiology Intestines - radiation effects Mice Models, Animal Paneth Cells - cytology Paneth Cells - drug effects Paneth Cells - radiation effects Radiation, Ionizing Receptors, G-Protein-Coupled - metabolism Regeneration - drug effects Regeneration - radiation effects Stem Cells - cytology Stem Cells - drug effects Stem Cells - radiation effects
ISSN:	1875-9777, 1875-9777
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Abstract	The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5(-) reserve stem cells are radiosensitive and that Lgr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.
AbstractList	The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5(-) reserve stem cells are radiosensitive and that Lgr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5(-) reserve stem cells are radiosensitive and that Lgr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation. The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5(-) reserve stem cells are radiosensitive and that Lgr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.
Author	Kljavin, Noelyn M de Sauvage, Frederic J Metcalfe, Ciara Ybarra, Ryan
Author_xml	– sequence: 1 givenname: Ciara surname: Metcalfe fullname: Metcalfe, Ciara organization: Molecular Oncology Department, Genentech, South San Francisco, CA 94080, USA – sequence: 2 givenname: Noelyn M surname: Kljavin fullname: Kljavin, Noelyn M organization: Molecular Oncology Department, Genentech, South San Francisco, CA 94080, USA – sequence: 3 givenname: Ryan surname: Ybarra fullname: Ybarra, Ryan organization: Molecular Oncology Department, Genentech, South San Francisco, CA 94080, USA – sequence: 4 givenname: Frederic J surname: de Sauvage fullname: de Sauvage, Frederic J email: desauvage.fred@gene.com organization: Molecular Oncology Department, Genentech, South San Francisco, CA 94080, USA. Electronic address: desauvage.fred@gene.com
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24332836$$D View this record in MEDLINE/PubMed
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PublicationTitle	Cell stem cell
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References	24506878 - Cell Stem Cell. 2014 Feb 6;14(2):135-6
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Snippet	The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs)....
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SubjectTerms	Adenomatous Polyposis Coli Protein - metabolism Animals Colitis - chemically induced Colitis - pathology Dextran Sulfate Diphtheria Toxin - pharmacology Dose-Response Relationship, Radiation Hyperplasia Intestines - drug effects Intestines - physiology Intestines - radiation effects Mice Models, Animal Paneth Cells - cytology Paneth Cells - drug effects Paneth Cells - radiation effects Radiation, Ionizing Receptors, G-Protein-Coupled - metabolism Regeneration - drug effects Regeneration - radiation effects Stem Cells - cytology Stem Cells - drug effects Stem Cells - radiation effects
Title	Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration
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