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Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice

In response to ionizing radiation-induced injury, the normally quiescent intestinal stem cells marked by BMI1 participate in the regenerative response. Previously, we established a protective role for Krüppel-like factor 4 (KLF4) in the intestinal epithelium where it reduces senescence, apoptosis, a...

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Autores principales: Kuruvilla, Jes G., Kim, Chang-Kyung, Ghaleb, Amr M., Bialkowska, Agnieszka B., Kuo, Calvin J., Yang, Vincent W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911500/
https://www.ncbi.nlm.nih.gov/pubmed/27237377
http://dx.doi.org/10.1016/j.stemcr.2016.04.014
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author Kuruvilla, Jes G.
Kim, Chang-Kyung
Ghaleb, Amr M.
Bialkowska, Agnieszka B.
Kuo, Calvin J.
Yang, Vincent W.
author_facet Kuruvilla, Jes G.
Kim, Chang-Kyung
Ghaleb, Amr M.
Bialkowska, Agnieszka B.
Kuo, Calvin J.
Yang, Vincent W.
author_sort Kuruvilla, Jes G.
collection PubMed
description In response to ionizing radiation-induced injury, the normally quiescent intestinal stem cells marked by BMI1 participate in the regenerative response. Previously, we established a protective role for Krüppel-like factor 4 (KLF4) in the intestinal epithelium where it reduces senescence, apoptosis, and crypt atrophy following γ-radiation-induced gut injury. We also described a pro-proliferative function for KLF4 during the regenerative phase post irradiation. In the current study, using a mouse model in which Klf4 is deleted from quiescent BMI1(+) intestinal stem cells, we observed increased proliferation from the BMI1(+) lineage during homeostasis. In contrast, following irradiation, Bmi1-specific Klf4 deletion leads to decreased expansion of the BMI1(+) lineage due to a combination of reduced proliferation and increased apoptosis. Our results support a critical role for KLF4 in modulating BMI1(+) intestinal stem cell fate in both homeostasis and the regenerative response to radiation injury.
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spelling pubmed-49115002016-06-28 Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice Kuruvilla, Jes G. Kim, Chang-Kyung Ghaleb, Amr M. Bialkowska, Agnieszka B. Kuo, Calvin J. Yang, Vincent W. Stem Cell Reports Report In response to ionizing radiation-induced injury, the normally quiescent intestinal stem cells marked by BMI1 participate in the regenerative response. Previously, we established a protective role for Krüppel-like factor 4 (KLF4) in the intestinal epithelium where it reduces senescence, apoptosis, and crypt atrophy following γ-radiation-induced gut injury. We also described a pro-proliferative function for KLF4 during the regenerative phase post irradiation. In the current study, using a mouse model in which Klf4 is deleted from quiescent BMI1(+) intestinal stem cells, we observed increased proliferation from the BMI1(+) lineage during homeostasis. In contrast, following irradiation, Bmi1-specific Klf4 deletion leads to decreased expansion of the BMI1(+) lineage due to a combination of reduced proliferation and increased apoptosis. Our results support a critical role for KLF4 in modulating BMI1(+) intestinal stem cell fate in both homeostasis and the regenerative response to radiation injury. Elsevier 2016-05-26 /pmc/articles/PMC4911500/ /pubmed/27237377 http://dx.doi.org/10.1016/j.stemcr.2016.04.014 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Report
Kuruvilla, Jes G.
Kim, Chang-Kyung
Ghaleb, Amr M.
Bialkowska, Agnieszka B.
Kuo, Calvin J.
Yang, Vincent W.
Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice
title Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice
title_full Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice
title_fullStr Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice
title_full_unstemmed Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice
title_short Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice
title_sort krüppel-like factor 4 modulates development of bmi1(+) intestinal stem cell-derived lineage following γ-radiation-induced gut injury in mice
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911500/
https://www.ncbi.nlm.nih.gov/pubmed/27237377
http://dx.doi.org/10.1016/j.stemcr.2016.04.014
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