The Cellular Perspective on Mammary Gland Development: Stem/Progenitor Cells and Beyond

Abstract

Study of the mammary gland at the stem cell level is necessary for understanding mammary gland development. Knowledge of mammary gland development and growth is the first step toward formulating strategies to improve milk production. The success of these strategies requires an understanding of the dynamics of adult stem cells and their progeny in the development of the bovine mammary gland. The stem cell lineage pathway begins with adult stem cells and ends with the production of terminally differentiated cells. The progression of adult stem cells along the mammary gland stem cell lineage pathway requires the coordination of many events. One important event in this process is cell differentiation. This differentiation process evolves with a gradient appearance of cell organelles progressing from stem cells to terminally differentiated cells. To dissect differentiation, mechanisms that regulate stem cells to differentiate toward a particular cell fate must be identified. Ultrastructural characteristics assist in distinguishing cells in various stages of differentiation in the mammary gland cell lineage pathway. Cells in the lineage pathway can become either epithelial cells or myoepithelial cells. Epithelial cells function in the production and secretion of milk, whereas myoepithelial cells assist epithelial cells in milk secretion. This review focuses on current concepts regarding adult stem cells and the recent progress on bovine mammary gland stem/progenitor cell development and differentiation. Multistep strategies that incorporate manipulation of the mechanisms influencing lineage choices in the mammary gland will produce beneficial effects on mammary gland development and milk production.

Mammary Stem Cell Research in Veterinary Science: An Update

“…Moreover, these cells immunohistochemically expressed casein, but not connexin 43, a gap junction protein [52]. This group named these cells bovine mammary gland progenitor cells or BMGPC [14,53]. A couple of years later, Capuco identified putative bovine MaSC by their retention of labeled DNA strands and characterized these cells more thoroughly based on the expression of the nuclear proliferation antigen Ki67 and estrogen receptor (ER)/progesterone receptor (PR) expression [51].…”

“…The luminal epithelium forms the ducts and the secretory alveoli, whereas the basal epithelium consists of myoepithelial cells [13][14][15]. It has been suggested that all these differentiated mammary cells, which possess different morphologies, characteristics, and potency, are derived from mammary gland stem cells [16][17][18].…”

Isolation and Culture of Bovine Mammary Epithelial Stem Cells

“…There are some other similarities between mouse, human and bovine MESCs. Mammary epithelial cells from the human and mouse have been identified as type I and type II cells in cell culture experiments [15,16], and research on the cytology of bovine tissue sections designates the cells as small and large cells [9,4]. Chepko et al and Holland et al found that the type I cells consist of undifferentiated small light cells and undifferentiated large light cells and suggested that undifferentiated small light cells contain both stem and primary progenitor cells [3,14].…”

“…Human and mouse mammary epithelial cells have been identified as type I and type II cells [17,18]. In bovine, these mammary epithelial cells have been identified as small light cells (SLC), large dark cells (LDC) and large light cells (LLC) [3,15]. Examination of the mammary gland stem cell at the light and ultrastructural level has revealed many similarities between mouse, human and bovine cells, with the type I cells consisting of undifferentiated SLCs and LLCs.…”

Expression of a putative stem cell marker, Musashi 1, in mammary glands of ewes

“…There are increasing number of papers and evidences that characterize mammary gland stem cells in dairy animals, primarily on cows (Chepko and Smith 1999;Ellis and Capuco 2002;Holland et al 2003;Capuco 2007). These identifications are mostly based on ultrastructural studies, and on the ability of stem cells to efflux cellular dyes, or to retain labeled DNA strands; therefore, they are designated as label-retaining cells (LRC) (Capuco 2007;Holland and Holland 2005;Welm et al 2003). These cells express the neuroglial stem cell marker Musashi 1 (Msi 1) (Clarke et al , 2005, an RNA-binding protein, which was originally identified as a positive regulator of Notch signalling (Imai et al 2001) and a cell fate determinant in the central nervous system stem cells (Sakakibara et al 1996.…”