Ndy Hayes, Leo Zeef and Peter March in the Genomic Technologies, Bioinformatics and Bioimaging facilities, and Fiona Foster for advice; Alan 3-Bromopyruvic acid web Whitmarsh, Amanda O’Donnell and members of our laboratory for comments on the manuscript and stimulating discussions; and Charles Streuli’s lab for reagents.GABPA and Cell Migration ControlAuthor ContributionsConceived and designed the experiments: ZO ADS. Performed the experiments: ZO. Analyzed the data: ZO ADS. Contributed reagents/ materials/analysis tools: ZO. Wrote the paper: ZO ADS.
It is important to understand the specific response of somatic stem cells to genotoxic exposure, especially in comparison to the cell majority in tissues. Stem cell function is uniquely associated with regeneration, aging and wound repair responses, and these cells may serve as precursor cells during tumor development [1]. Various somatic stem cells have been tested for their response to genotoxic damage, including hematopoetic stem cells, neural stem cells, the epidermal stem cells of the follicular bulge, and melanocytes. In the examples studied to date, stem cells undergo a range of responses to genotoxic exposure, from resistance, to senescence, death by apoptosis, or differentiation. These responses likely illustrate the compromises that are made for each specific tissue to maximize success of the animal. Thus, the preservation of essential stem cells in tissues with a high turnover rate may come at the price of genetic integrity, and the resistance to tumor development offered by the elimination of mutant stem cells may be offset by premature aging [2,3,4,5,6,7,8]. In this study, we 1480666 evaluated the response of mammary stem cells to genotoxic exposure during juvenile development. The cellautonomous stem cell activity characterized (so far) for mammary gland copurifies with one of the two Castanospermine principal epithelial lineages, the basal(/myoepithelial) cell population [9,10]; thus afterdissociation of mammary epithelial cells from 1676428 the mammary ducts, a single basal cell can regenerate a whole mammary gland. Cells from the luminal population (responsible for milk secretion and the perception of the dominant estrogen growth signal) cannot reconstitute mammary gland, but this population does include progenitors that can generate limited outgrowths, and function as unipotent stem cells in vivo [11]. The overall frequency of ductal basal stem cells in mammary gland is at least 1/1600 (results from this study, these frequencies vary from strain to strain, and are tentative given that cell dissociation is likely to compromise functional activity). These cells cannot yet be recognized in situ, since there is no marker that can distinguish stem cells from the rest. There are two phases of growth in the mammary gland, one that establishes the ductal tree during peri-puberty, and another during pregnancy that serves to fill the space between the ducts with lobuloalveolar units. Neither basal nor luminal cells are “terminally differentiated” since both divide at about the same rate during these processes [12]. For this study, we tested the effect of genotoxic exposure during juvenile growth. The cells born during ductal outgrowth are long-lived, compared to the majority that are born and die during pregnancy and estrus. For this study, we selected a representative of the polycyclic aromatic hydrocarbons, DMBA (dimethylbenz[a]anthracene) asGenotoxins Inhibit Wnt-Dependent Mammary Stem Cellthe genotoxin. This group of compounds are e.Ndy Hayes, Leo Zeef and Peter March in the Genomic Technologies, Bioinformatics and Bioimaging facilities, and Fiona Foster for advice; Alan Whitmarsh, Amanda O’Donnell and members of our laboratory for comments on the manuscript and stimulating discussions; and Charles Streuli’s lab for reagents.GABPA and Cell Migration ControlAuthor ContributionsConceived and designed the experiments: ZO ADS. Performed the experiments: ZO. Analyzed the data: ZO ADS. Contributed reagents/ materials/analysis tools: ZO. Wrote the paper: ZO ADS.
It is important to understand the specific response of somatic stem cells to genotoxic exposure, especially in comparison to the cell majority in tissues. Stem cell function is uniquely associated with regeneration, aging and wound repair responses, and these cells may serve as precursor cells during tumor development [1]. Various somatic stem cells have been tested for their response to genotoxic damage, including hematopoetic stem cells, neural stem cells, the epidermal stem cells of the follicular bulge, and melanocytes. In the examples studied to date, stem cells undergo a range of responses to genotoxic exposure, from resistance, to senescence, death by apoptosis, or differentiation. These responses likely illustrate the compromises that are made for each specific tissue to maximize success of the animal. Thus, the preservation of essential stem cells in tissues with a high turnover rate may come at the price of genetic integrity, and the resistance to tumor development offered by the elimination of mutant stem cells may be offset by premature aging [2,3,4,5,6,7,8]. In this study, we 1480666 evaluated the response of mammary stem cells to genotoxic exposure during juvenile development. The cellautonomous stem cell activity characterized (so far) for mammary gland copurifies with one of the two principal epithelial lineages, the basal(/myoepithelial) cell population [9,10]; thus afterdissociation of mammary epithelial cells from 1676428 the mammary ducts, a single basal cell can regenerate a whole mammary gland. Cells from the luminal population (responsible for milk secretion and the perception of the dominant estrogen growth signal) cannot reconstitute mammary gland, but this population does include progenitors that can generate limited outgrowths, and function as unipotent stem cells in vivo [11]. The overall frequency of ductal basal stem cells in mammary gland is at least 1/1600 (results from this study, these frequencies vary from strain to strain, and are tentative given that cell dissociation is likely to compromise functional activity). These cells cannot yet be recognized in situ, since there is no marker that can distinguish stem cells from the rest. There are two phases of growth in the mammary gland, one that establishes the ductal tree during peri-puberty, and another during pregnancy that serves to fill the space between the ducts with lobuloalveolar units. Neither basal nor luminal cells are “terminally differentiated” since both divide at about the same rate during these processes [12]. For this study, we tested the effect of genotoxic exposure during juvenile growth. The cells born during ductal outgrowth are long-lived, compared to the majority that are born and die during pregnancy and estrus. For this study, we selected a representative of the polycyclic aromatic hydrocarbons, DMBA (dimethylbenz[a]anthracene) asGenotoxins Inhibit Wnt-Dependent Mammary Stem Cellthe genotoxin. This group of compounds are e.
