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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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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. |
format | Online Article Text |
id | pubmed-4911500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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