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The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction
Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. We now demonstrate that a phenotypically defined cell population enriched in luminal progenitors (LPs) is characterized by unusually short telomeres independently of donor age...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757746/ https://www.ncbi.nlm.nih.gov/pubmed/24052939 http://dx.doi.org/10.1016/j.stemcr.2013.04.003 |
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author | Kannan, Nagarajan Huda, Nazmul Tu, LiRen Droumeva, Radina Aubert, Geraldine Chavez, Elizabeth Brinkman, Ryan R. Lansdorp, Peter Emerman, Joanne Abe, Satoshi Eaves, Connie Gilley, David |
author_facet | Kannan, Nagarajan Huda, Nazmul Tu, LiRen Droumeva, Radina Aubert, Geraldine Chavez, Elizabeth Brinkman, Ryan R. Lansdorp, Peter Emerman, Joanne Abe, Satoshi Eaves, Connie Gilley, David |
author_sort | Kannan, Nagarajan |
collection | PubMed |
description | Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. We now demonstrate that a phenotypically defined cell population enriched in luminal progenitors (LPs) is characterized by unusually short telomeres independently of donor age. Furthermore, we find that multiple DNA damage response proteins colocalize with telomeres in >95% of LPs but in <5% of basal cells. Paradoxically, 25% of LPs are still capable of exhibiting robust clonogenic activity in vitro. This may be partially explained by the elevated telomerase activity that was also seen only in LPs. Interestingly, this potential telomere salvage mechanism declines with age. Our findings thus reveal marked differences in the telomere biology of different subsets of primitive normal human mammary cells. The chronically dysfunctional telomeres unique to LPs have potentially important implications for normal mammary tissue homeostasis as well as the development of certain breast cancers. |
format | Online Article Text |
id | pubmed-3757746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-37577462013-09-17 The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction Kannan, Nagarajan Huda, Nazmul Tu, LiRen Droumeva, Radina Aubert, Geraldine Chavez, Elizabeth Brinkman, Ryan R. Lansdorp, Peter Emerman, Joanne Abe, Satoshi Eaves, Connie Gilley, David Stem Cell Reports Report Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. We now demonstrate that a phenotypically defined cell population enriched in luminal progenitors (LPs) is characterized by unusually short telomeres independently of donor age. Furthermore, we find that multiple DNA damage response proteins colocalize with telomeres in >95% of LPs but in <5% of basal cells. Paradoxically, 25% of LPs are still capable of exhibiting robust clonogenic activity in vitro. This may be partially explained by the elevated telomerase activity that was also seen only in LPs. Interestingly, this potential telomere salvage mechanism declines with age. Our findings thus reveal marked differences in the telomere biology of different subsets of primitive normal human mammary cells. The chronically dysfunctional telomeres unique to LPs have potentially important implications for normal mammary tissue homeostasis as well as the development of certain breast cancers. Elsevier 2013-06-04 /pmc/articles/PMC3757746/ /pubmed/24052939 http://dx.doi.org/10.1016/j.stemcr.2013.04.003 Text en © 2013 The Authors http://creativecommons.org/licenses/by/3.0/ 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 credited. |
spellingShingle | Report Kannan, Nagarajan Huda, Nazmul Tu, LiRen Droumeva, Radina Aubert, Geraldine Chavez, Elizabeth Brinkman, Ryan R. Lansdorp, Peter Emerman, Joanne Abe, Satoshi Eaves, Connie Gilley, David The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction |
title | The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction |
title_full | The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction |
title_fullStr | The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction |
title_full_unstemmed | The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction |
title_short | The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction |
title_sort | luminal progenitor compartment of the normal human mammary gland constitutes a unique site of telomere dysfunction |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757746/ https://www.ncbi.nlm.nih.gov/pubmed/24052939 http://dx.doi.org/10.1016/j.stemcr.2013.04.003 |
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