Stem Cells and the Developing Mammary Gland
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The mammary gland undergoes dynamic changes throughout life. In the mouse, these begin with initial morphogenesis of the gland in the mid-gestation embryo followed by hormonally regulated changes during puberty and later in adulthood. The adult mammary gland contains a hierarchy of cell types with varying potentials for self-maintenance and differentiation. These include cells able to produce complete, functional mammary glands in vivo and that contain daughter cells with the same remarkable regenerative potential, as well as cells with more limited clonogenic activity in vitro. Here we review how applying in vitro and in vivo methods for quantifying these cells in adult mammary tissue to fetal mammary cells has enabled the first cells fulfilling the functional criteria of transplantable, isolated mammary stem cells to be identified a few days before birth. Thereafter, the number of these cells increases rapidly. Populations containing these fetal stem cells display growth and gene expression programs that differ from their adult counterparts but share signatures characteristic of certain types of breast cancer. Such observations reinforce growing evidence of important differences between tissue-specific fetal and adult cells with stem cell properties and emphasize the merits of investigating their molecular basis.
KeywordsStem cells Progenitors Mammary gland Fetal Development Transcriptomes Breast cancer
Epidermal growth factor
Epithelial cell adhesion molecule
Fibroblast growth factor
Mammary repopulating unit
CE received support from the Canadian Breast Cancer Research Alliance with funds from the Canadian Cancer Society and from the British Columbia and Yukon Division of the Canadian Breast Cancer Foundation (BC-Y CBCF). MM held a Canadian Institutes of Health Research Studentship and NK a BC-Y CBCF Fellowship. CD was supported by T32 post-doctoral training grant 2T32CA009370; BTS was partially supported by T32 grant CA009523 and GW received support from the Breast Cancer Research Foundation, Susan G. Komen for the Cure, the Department of Defense BCRP, and many studies were enabled by Cores supported by Cancer Center Support Grant NCI 5P30CA014195. We also wish to acknowledge the many other important contributors to this field whose papers we could not reference due to space constraints.
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