TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Plasticity of mammary development in the prepubertal bovine mammary gland1,2

Akers, R.M.

doi:10.2527/jas2017.1792

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…The phase of pre-pubertal development of the bovine mammary gland has been highlighted as a developmental period that impacts future lactational productivity 23 , 24 and a number of studies have provided valuable insights into pre-pregnancy development of the bovine udder, including the effect of plane of nutrition on its development 25 . To assess epithelial proliferation in the bovine mammary gland, bromodeoxyuridine (BrdU) incorporation studies have been performed, and these have revealed cell proliferation to be higher in the peripheral parenchymal zone than adjacent to the developing gland cistern 26 , 27 .…”

Section: Introductionmentioning

confidence: 99%

Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

et al. 2021

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The human breast and ovine mammary gland undergo striking levels of postnatal development, leading to formation of terminal duct lobular units (TDLUs). Here we interrogate aspects of sheep TDLU growth as a model of breast development and to increase understanding of ovine mammogenesis. The distributions of epithelial nuclear Ki67 positivity differ significantly between younger and older lambs. Ki67 expression is polarised to the leading edge of the developing TDLUs. Intraepithelial ductal macrophages exhibit periodicity and considerably increased density in lambs approaching puberty. Stromal macrophages are more abundant centrally than peripherally. Intraepithelial T lymphocytes are more numerous in older lambs. Stromal hotspots of Ki67 expression colocalize with immune cell aggregates that exhibit distinct organisation consistent with tertiary lymphoid structures. The lamb mammary gland thus exhibits a dynamic mucosal and stromal immune microenvironment and constitutes a valuable model system that provides new insights into postnatal breast development.

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Section: Introductionmentioning

confidence: 99%

Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

et al. 2021

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“…This suggests that the full repertoire of systemic and niche-dependent stimuli necessary for full differentiation of the epithelial stem cell toward a functional luminal cell already exists at this early developmental stage. Their activity in prepuberty dictates future productivity of the mammary gland [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Intramammary rapamycin administration to calves induces epithelial stem cell self-renewal and latent cell proliferation and milk protein expression

Kosenko

Jacoby²,

Ross³

et al. 2022

PLoS ONE

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Mammary epithelial stem cells differentiate to create the basal and luminal layers of the gland. Inducing the number of differentiating bovine mammary stem cells may provide compensating populations for the milk-producing cells that die during lactation. Inhibition of mTOR activity by rapamycin signals self-renewal of intestinal stem cells, with similar consequences in the mouse mammary gland and in bovine mammary implants maintained in mice. The implementation of these results in farm animals for better mammary development and production was studied in 3-month-old calves. mTOR activity decreased by ~50% in mammary epithelial cells subjected to 3-week rapamycin administration, with no negative consequences on mammary morphology or β-casein expression. Subsequently, stem cell self-renewal was induced, reflected by a higher propagation rate of cultures from rapamycin-treated glands compared to respective controls and higher expression of selected markers. Followed by 4-day estrogen and progesterone administration, rapamycin significantly induced proliferation rate. Higher numbers of basal and luminal PCNA+ cells were detected in small ducts near the elongating sites as compared to large ducts, in which only luminal cells were affected. Rapamycin administration resulted in induction of individual milk protein genes’ expression, which was negatively correlated to their endogenous levels. The inductive effect of rapamycin on luminal cell number was confirmed in organoid cultures, but milk protein expression decreased, probably due to lack of oscillation in rapamycin levels. In conclusion, intramammary rapamycin administration is an effective methodology to reduce mTOR activity in bovine mammary epithelial cells and consequently, induce stem cell self-renewal. The latent positive effect of rapamycin on epithelial cell proliferation and its potential to improve milk protein expression in calves may have beneficial implications for mature cows.

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“…The molecular patterns (e.g., gene expression) of some mammary cell types have been described at the population level in dairy cows [6][7][8]. However, little is known about the cell lineage speci cation in the bovine MG, and a comprehensive understanding of the heterogeneity within the different bovine mammary cell populations is lacking.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA-Aequencing Reveals Novel Myofibroblasts with Epithelial Cell-Like Features in the Mammary Gland of Dairy Cattle

Gu¹,

Wu²,

Zhu³

et al. 2020

Preprint

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Background: Cow’s milk is a highly-nutritious dairy product that is widely consumed worldwide. It is secreted by the developed mammary gland (MG) of dairy cattle. However, a comprehensive understanding of cell-type diversity and cell function within bovine MG is lacking. In the current study, we used single-cell RNA sequencing to investigate the transcriptome of 24,472 high-quality MG cells isolated from newborn and adult cows. Results: Unbiased clustering analysis revealed the existence of 24 cell types, which could be divided into four categories: 9 immune, 3 epithelial, 9 fibroblast, and 3 endothelial cell types. Other cell subtypes were further identified based on re-clustering and pseudotemporal reconstruction of epithelial cells that included 3 mature luminal epithelial, 1 intermediate, and 2 progenitor cell subtypes. The individual top marker genes of these 3 mature luminal epithelial cell subtypes (L0, L1, and L5) were APOA1, STC2, and PTX3, which were further validated using immunofluorescence. Based on functional analysis, the L0, L1, and L5 cell subtypes were all involved in the upregulation of lipid metabolism, protein and hormone metabolism, and the immune response, respectively. Furthermore, we discovered a novel myofibroblast that expresses COL1A1 and CSN3, has visible epithelial-like characteristics, and shows the potential to differentiate into luminal epithelial cells, especially immune-sensing luminal cells (L5). Conclusions: We constructed the first single-cell atlas of the dairy cow MG, and our new findings of epithelial-like myofibroblast cells and their differentiation trajectories into luminal cells may provide novel insights into the development and lactogenesis in dairy cattle MGs.

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TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Plasticity of mammary development in the prepubertal bovine mammary gland1,2

Cited by 7 publications

References 72 publications

Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

Intramammary rapamycin administration to calves induces epithelial stem cell self-renewal and latent cell proliferation and milk protein expression

Single-cell RNA-Aequencing Reveals Novel Myofibroblasts with Epithelial Cell-Like Features in the Mammary Gland of Dairy Cattle

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