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Title:
Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland | Breast Cancer Research
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Introduction Studies have identified multi-potent stem cells in the adult mammary gland. More recent studies have suggested that the embryonic mammary gland may also contain stem/progenitor cells that contribute to initial ductal development. We were interested in determining whether embryonic cells might also directly contribute to long-lived stem cells that support homeostasis and development in the adult mammary gland. Methods We used DNA-label retention to detect long label-retaining cells in the mammary gland. Mouse embryos were labeled with 5-ethynl-2β²-deoxyuridine (EdU) between embryonic day 14.5 and embryonic day 18.5 and were subsequently sacrificed and examined for EdU retention at various intervals after birth. EdU retaining cells were co-stained for various lineage markers and identified after fluorescence activated cell sorting analysis of specific epithelial subsets. EdU-labeled mice were subjected to subsequent 5-bromo-2β²-deoxyuridine administration to determine whether EdU-labeled cells could re-enter the cell cycle. Finally, EdU-labeled cells were grown under non-adherent conditions to assess their ability to form mammospheres. Results We demonstrate embryonically-derived, long label-retaining cells (eLLRCs) in the adult mammary gland. eLLRCs stain for basal markers and are enriched within the mammary stem cell population identified by cell sorting. eLLRCs are restricted to the primary ducts near the nipple region. Interestingly, long label retaining cells (labeled during puberty) are found just in front of the eLLRCs, near where the ends of the ducts had been at the time of DNA labeling in early puberty. A subset of eLLRCs becomes mitotically active during periods of mammary growth and in response to ovarian hormones. Finally, we show that eLLRCs are contained within primary and secondary mammospheres. Conclusions Our findings suggest that a subset of proliferating embryonic cells subsequently becomes quiescent and contributes to the pool of long-lived mammary stem cells in the adult. eLLRCs can re-enter the cell cycle, produce both mammary lineages and self-renew. Thus, our studies have identified a putative stem/progenitor cell population of embryonic origin. Further study of these cells will contribute to an understanding of how quiescent stem cells are generated during development and how fetal exposures may alter future breast cancer risk in adults.
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Keywords {π}
cells, mammary, gland, cell, ellrcs, stem, embryonic, pubmed, luminal, figure, basal, article, development, epithelial, google, scholar, brdu, adult, cas, label, labeling, ducts, stemprogenitor, studies, markers, mice, mammospheres, quiescent, weeks, lineage, ductal, days, edupositive, analysis, data, contribute, labeled, population, glands, mouse, long, day, puberty, region, growth, lineages, embryonically, facs, llrcs, authors,
Topics {βοΈ}
wnt/Ξ²-catenin-responsive stem cells long-term stem/progenitor cells long-lived stem/progenitor cells bi-potent stem/progenitor cells lin-cd24+cd49fhigh basal cells long-term double-labeled cells long-label-retaining mammary cells sorted lin-cd24+cd49flow luminal article download pdf embryonically-derived stem cells long-lived stem cells quiescent stem/progenitor cell mammary stem/progenitor cells stem/progenitor cell compartments post-natal mammary gland lin-cd24+cd49fhigh basal mammary stem/prognitor cells simply represent post-mitotic quiescent stem/progenitor cells lin-cd24+cd49flow luminal lin-cd24+cd49flo luminal long label-retaining cells fcΞ³ iii/ii receptor adipocyte-rich stromal compartment basal stem/progenitor cells article boras-granic asselin-labat m embryonically-derived cells contribute label-retaining epithelial cells stem cell-enriched population nuclear label-retaining cells support long-term homeostasis brdu-retaining epithelial cells brdu label-retaining cells double-labeled cells represent developmental stage-specific contribution kata boras-granic lineage-restricted progenitor cells van kappel ec cell stem cell stem/progenitor cells expected cell-surface phenotype mammary stem cell previous cell sorting epithelial stem cell slowly cycling cells embryonically derived cells human breast cancer mammary stem cells significant stem cell
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- Soto AM, Brisken C, Schaeberle C, Sonnenschein C: Does cancer start in the womb?
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headline:Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland
description:Studies have identified multi-potent stem cells in the adult mammary gland. More recent studies have suggested that the embryonic mammary gland may also contain stem/progenitor cells that contribute to initial ductal development. We were interested in determining whether embryonic cells might also directly contribute to long-lived stem cells that support homeostasis and development in the adult mammary gland. We used DNA-label retention to detect long label-retaining cells in the mammary gland. Mouse embryos were labeled with 5-ethynl-2β²-deoxyuridine (EdU) between embryonic day 14.5 and embryonic day 18.5 and were subsequently sacrificed and examined for EdU retention at various intervals after birth. EdU retaining cells were co-stained for various lineage markers and identified after fluorescence activated cell sorting analysis of specific epithelial subsets. EdU-labeled mice were subjected to subsequent 5-bromo-2β²-deoxyuridine administration to determine whether EdU-labeled cells could re-enter the cell cycle. Finally, EdU-labeled cells were grown under non-adherent conditions to assess their ability to form mammospheres. We demonstrate embryonically-derived, long label-retaining cells (eLLRCs) in the adult mammary gland. eLLRCs stain for basal markers and are enriched within the mammary stem cell population identified by cell sorting. eLLRCs are restricted to the primary ducts near the nipple region. Interestingly, long label retaining cells (labeled during puberty) are found just in front of the eLLRCs, near where the ends of the ducts had been at the time of DNA labeling in early puberty. A subset of eLLRCs becomes mitotically active during periods of mammary growth and in response to ovarian hormones. Finally, we show that eLLRCs are contained within primary and secondary mammospheres. Our findings suggest that a subset of proliferating embryonic cells subsequently becomes quiescent and contributes to the pool of long-lived mammary stem cells in the adult. eLLRCs can re-enter the cell cycle, produce both mammary lineages and self-renew. Thus, our studies have identified a putative stem/progenitor cell population of embryonic origin. Further study of these cells will contribute to an understanding of how quiescent stem cells are generated during development and how fetal exposures may alter future breast cancer risk in adults.
datePublished:2014-12-03T00:00:00Z
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Mammary Gland
Mammary Stem Cell
Fluorescence Activate Cell Sorting Analysis
Quiescent Stem Cell
Luminal Marker
Cancer Research
Oncology
Surgical Oncology
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headline:Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland
description:Studies have identified multi-potent stem cells in the adult mammary gland. More recent studies have suggested that the embryonic mammary gland may also contain stem/progenitor cells that contribute to initial ductal development. We were interested in determining whether embryonic cells might also directly contribute to long-lived stem cells that support homeostasis and development in the adult mammary gland. We used DNA-label retention to detect long label-retaining cells in the mammary gland. Mouse embryos were labeled with 5-ethynl-2β²-deoxyuridine (EdU) between embryonic day 14.5 and embryonic day 18.5 and were subsequently sacrificed and examined for EdU retention at various intervals after birth. EdU retaining cells were co-stained for various lineage markers and identified after fluorescence activated cell sorting analysis of specific epithelial subsets. EdU-labeled mice were subjected to subsequent 5-bromo-2β²-deoxyuridine administration to determine whether EdU-labeled cells could re-enter the cell cycle. Finally, EdU-labeled cells were grown under non-adherent conditions to assess their ability to form mammospheres. We demonstrate embryonically-derived, long label-retaining cells (eLLRCs) in the adult mammary gland. eLLRCs stain for basal markers and are enriched within the mammary stem cell population identified by cell sorting. eLLRCs are restricted to the primary ducts near the nipple region. Interestingly, long label retaining cells (labeled during puberty) are found just in front of the eLLRCs, near where the ends of the ducts had been at the time of DNA labeling in early puberty. A subset of eLLRCs becomes mitotically active during periods of mammary growth and in response to ovarian hormones. Finally, we show that eLLRCs are contained within primary and secondary mammospheres. Our findings suggest that a subset of proliferating embryonic cells subsequently becomes quiescent and contributes to the pool of long-lived mammary stem cells in the adult. eLLRCs can re-enter the cell cycle, produce both mammary lineages and self-renew. Thus, our studies have identified a putative stem/progenitor cell population of embryonic origin. Further study of these cells will contribute to an understanding of how quiescent stem cells are generated during development and how fetal exposures may alter future breast cancer risk in adults.
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Mammary Gland
Mammary Stem Cell
Fluorescence Activate Cell Sorting Analysis
Quiescent Stem Cell
Luminal Marker
Cancer Research
Oncology
Surgical Oncology
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