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

Ewa Osińska,Karol Pawłowski,Michał M Godlewski,Alicja Majewska,Zofia Wicik,Tomasz Motyl,Joanna Mucha,Małgorzata Gajewska

doi:10.1007/s13353-014-0213-1

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-1posFNDC3Bpos 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.

Highlights

The bovine mammary gland is a unique organ with regard to its frequently repeating cycles of growth and involution throughout the life of an animal
The results demonstrated that bovine mammary epithelial cells expressing stem cell antigen-1 (Sca-1) comprised about 2 % of the total cell number in the mammary tissue
The classification of genes according to their molecular function revealed four major groups of up-regulated genes in HF heifers: transcription regulator activity (53 genes), cytokine activity (17 genes), growth factor activity (12 genes), and chemokine activity (9 genes)

Summary

Introduction

The bovine mammary gland is a unique organ with regard to its frequently repeating cycles of growth and involution throughout the life of an animal. The general processes controlling mammogenesis have been extensively studied, the knowledge on the role of stem cells and their renewal during mammary gland development is still insufficient. Mammary stem cells (MaSC) are defined as cells that can generate the ductal and lobular components of the mammary epithelial tree, complete with all the cell types of the mammary epithelium, as well as having the ability to self-renew (Stingl 2009). Stem cells allow the mammary epithelium to expand intensively during puberty and pregnancy, preparing the gland for milk production and secretion during lactation (Daniel and Smith 1999). Until now, a universal molecular stem cell marker for the identification of these cells has not been found. The most successful approach used to identify mouse MaSC has been based on a combination of surface markers: CD24 (heat-stable antigen), CD29 (β1 integrin), CD49f (α6 integrin), CD61

Methods

Results

Conclusion