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c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells

BACKGROUND: Bronchoalveolar stem cells (BASCs) located in the bronchoalveolar duct junction are thought to regenerate both bronchiolar and alveolar epithelium during homeostatic turnover and in response to injury. The mechanisms directing self-renewal in BASCs are poorly understood. METHODS: BASCs (...

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Autores principales: Dong, Jie, Sutor, Shari, Jiang, Guoqian, Cao, Yajun, Asmann, Yan W., Wigle, Dennis A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157444/
https://www.ncbi.nlm.nih.gov/pubmed/21858211
http://dx.doi.org/10.1371/journal.pone.0023707
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author Dong, Jie
Sutor, Shari
Jiang, Guoqian
Cao, Yajun
Asmann, Yan W.
Wigle, Dennis A.
author_facet Dong, Jie
Sutor, Shari
Jiang, Guoqian
Cao, Yajun
Asmann, Yan W.
Wigle, Dennis A.
author_sort Dong, Jie
collection PubMed
description BACKGROUND: Bronchoalveolar stem cells (BASCs) located in the bronchoalveolar duct junction are thought to regenerate both bronchiolar and alveolar epithelium during homeostatic turnover and in response to injury. The mechanisms directing self-renewal in BASCs are poorly understood. METHODS: BASCs (Sca-1(+), CD34(+), CD31(−) and, CD45(−)) were isolated from adult mouse lung using FACS, and their capacity for self-renewal and differentiation were demonstrated by immunostaining. A transcription factor network of 53 genes required for pluripotency in embryonic stem cells was assessed in BASCs, Kras-initiated lung tumor tissue, and lung organogenesis by real-time PCR. c-Myc was knocked down in BASCs by infection with c-Myc shRNA lentivirus. Comprehensive miRNA and mRNA profiling for BASCs was performed, and significant miRNAs and mRNAs potentially regulated by c-Myc were identified. We explored a c-Myc regulatory network in BASCs using a number of statistical and computational approaches through two different strategies; 1) c-Myc/Max binding sites within individual gene promoters, and 2) miRNA-regulated target genes. RESULTS: c-Myc expression was upregulated in BASCs and downregulated over the time course of lung organogenesis in vivo. The depletion of c-Myc in BASCs resulted in decreased proliferation and cell death. Multiple mRNAs and miRNAs were dynamically regulated in c-Myc depleted BASCs. Among a total of 250 dynamically regulated genes in c-Myc depleted BASCs, 57 genes were identified as potential targets of miRNAs through miRBase and TargetScan-based computational mapping. A further 88 genes were identified as potential downstream targets through their c-Myc binding motif. CONCLUSION: c-Myc plays a critical role in maintaining the self-renewal capacity of lung bronchoalveolar stem cells through a combination of miRNA and transcription factor regulatory networks.
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spelling pubmed-31574442011-08-19 c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells Dong, Jie Sutor, Shari Jiang, Guoqian Cao, Yajun Asmann, Yan W. Wigle, Dennis A. PLoS One Research Article BACKGROUND: Bronchoalveolar stem cells (BASCs) located in the bronchoalveolar duct junction are thought to regenerate both bronchiolar and alveolar epithelium during homeostatic turnover and in response to injury. The mechanisms directing self-renewal in BASCs are poorly understood. METHODS: BASCs (Sca-1(+), CD34(+), CD31(−) and, CD45(−)) were isolated from adult mouse lung using FACS, and their capacity for self-renewal and differentiation were demonstrated by immunostaining. A transcription factor network of 53 genes required for pluripotency in embryonic stem cells was assessed in BASCs, Kras-initiated lung tumor tissue, and lung organogenesis by real-time PCR. c-Myc was knocked down in BASCs by infection with c-Myc shRNA lentivirus. Comprehensive miRNA and mRNA profiling for BASCs was performed, and significant miRNAs and mRNAs potentially regulated by c-Myc were identified. We explored a c-Myc regulatory network in BASCs using a number of statistical and computational approaches through two different strategies; 1) c-Myc/Max binding sites within individual gene promoters, and 2) miRNA-regulated target genes. RESULTS: c-Myc expression was upregulated in BASCs and downregulated over the time course of lung organogenesis in vivo. The depletion of c-Myc in BASCs resulted in decreased proliferation and cell death. Multiple mRNAs and miRNAs were dynamically regulated in c-Myc depleted BASCs. Among a total of 250 dynamically regulated genes in c-Myc depleted BASCs, 57 genes were identified as potential targets of miRNAs through miRBase and TargetScan-based computational mapping. A further 88 genes were identified as potential downstream targets through their c-Myc binding motif. CONCLUSION: c-Myc plays a critical role in maintaining the self-renewal capacity of lung bronchoalveolar stem cells through a combination of miRNA and transcription factor regulatory networks. Public Library of Science 2011-08-17 /pmc/articles/PMC3157444/ /pubmed/21858211 http://dx.doi.org/10.1371/journal.pone.0023707 Text en Dong et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dong, Jie
Sutor, Shari
Jiang, Guoqian
Cao, Yajun
Asmann, Yan W.
Wigle, Dennis A.
c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells
title c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells
title_full c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells
title_fullStr c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells
title_full_unstemmed c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells
title_short c-Myc Regulates Self-Renewal in Bronchoalveolar Stem Cells
title_sort c-myc regulates self-renewal in bronchoalveolar stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157444/
https://www.ncbi.nlm.nih.gov/pubmed/21858211
http://dx.doi.org/10.1371/journal.pone.0023707
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