Comparison of stem/progenitor cell number and transcriptomic profile in the mammary tissue of dairy and beef breed heifers

Abstract

Bovine mammary stem cells (MaSC) are a source of ductal and lobulo-alveolar tissue during the development of the mammary gland and its remodeling in repeating lactation cycles. We hypothesize that the number of MaSC, their molecular properties, and interactions with their niche may be essential in order to determine the mammogenic potential in heifers. To verify this hypothesis, we compared the number of MaSC and the transcriptomic profile in the mammary tissue of 20-month-old, non-pregnant dairy (Holstein-Friesian, HF) and beef (Limousin, LM) heifers. For the identification and quantification of putative stem/progenitor cells in mammary tissue sections, scanning cytometry was used with a combination of MaSC molecular markers: stem cell antigen-1 (Sca-1) and fibronectin type III domain containing 3B (FNDC3B) protein. Cytometric analysis revealed a significantly higher number of Sca-1(pos)FNDC3B(pos) cells in HF (2.94 ± 0.35%) than in LM (1.72 ± 0.20%) heifers. In HF heifers, a higher expression of intramammary hormones, growth factors, cytokines, chemokines, and transcription regulators was observed. The model of mammary microenvironment favorable for MaSC was associated with the regulation of genes involved in MaSC maintenance, self-renewal, proliferation, migration, differentiation, mammary tissue remodeling, angiogenesis, regulation of adipocyte differentiation, lipid metabolism, and steroid and insulin signaling. In conclusion, the mammogenic potential in postpubertal dairy heifers is facilitated by a higher number of MaSC and up-regulation of mammary auto- and paracrine factors representing the MaSC niche.

Fig. 1

Proposed scheme of molecular regulation of the mammary stem cell microenvironment. The scheme illustrates specific dynamic regulations leading to increased potential of milk production. The stem cell niche in the mammary gland comprises mammary stem cells, as well as epithelial and myoepithelial cells, which are separated by basement membrane from adipocytes, fibroblasts, and blood vessels. The scheme was developed based on the comparison of transcriptomic profiles of mammary glands from Holstein-Friesian (HF) heifers and Limousin (LM) heifers. The names of genes regulating stem cell activity are shown in bold. The arrows indicate the direction of gene expression in dairy heifers in relation to beef heifers