Mammary Epithelial Cell Transcriptome Reveals Potential Roles of lncRNAs in Regulating Milk Synthesis Pathways in Jersey and Kashmiri Cattle

Author(s):  
Peerzada Tajamul Mumtaz ◽  
Basharat Bhat ◽  
Eveline M. Ibeagha-Awemu ◽  
Qamar Taban ◽  
Mengqi Wang ◽  
...  

Abstract Background Long noncoding RNAs (lncRNAs) are now proven as essential regulatory elements, playing diverse role in many biological processes including mammary gland development. However, little is known about their roles in bovine lactation process. There are very few reports available to date on the role of lncRNAs in lactation physiology and mammary glands development in cattle. Results To identify and characterize the roles of lncRNAs in bovine lactation, milk derived mammary epithelial cells (MEC) from Jersey (high milk producer) and Kashmiri cattle (low milk producer) at early, mid and late lactation stages were used. The lncRNA transcriptome of the samples (n=18) was studied using next generation RNA sequencing technology. 633 putative lncRNAs were identified, 76 of which were differentially expressed (DE) between comparison between the three stages of lactation. Additionally, 56 DE lncRNAs were identified from 9 Jersey and 9 Kashmir samples. Correlation of DE lncRNAs with protein-coding genes resulted in a comprehensive list of lncRNA-mRNA co-expressed pairs. Most of the DE lncRNAs showed positive correlations with protein coding genes in Jersey compared to Kashmiri cattle where they were mainly negatively correlated, which could be one of the underlying mechanisms responsible for the differential milking performance between the two breeds. In addition, a number of the DE lncRNAs were paired with the most DE milk quality genes like GPAM, LPL, ABCG2, etc. indicative of their potential regulatory effects on milk quality genes. KEGG pathways analysis of potential cis and trans target genes of DE lncRNAs indicated that 27 and 48 pathways were significantly enriched in Kashmiri and Jersey respectively, including mTOR signaling, PI3K-Akt signaling and RAP1 signaling pathways. These pathways have been proven to play key roles in lactation biology and mammary gland development. Conclusions Our study mapped the expression profiles of lncRNAs across lactation stages and their relationships with candidate genes related to milk quality and yield traits in Jersey and Kashmiri cattle. These findings provide a valuable resource for the study of the regulatory mechanisms involved in the lactation process as well as facilitate understanding of the role of lncRNAs in bovine lactation biology.

2004 ◽  
Vol 15 (5) ◽  
pp. 2302-2311 ◽  
Author(s):  
Yijun Yi ◽  
Anne Shepard ◽  
Frances Kittrell ◽  
Biserka Mulac-Jericevic ◽  
Daniel Medina ◽  
...  

This study demonstrated, for the first time, the following events related to p19ARFinvolvement in mammary gland development: 1) Progesterone appears to regulate p19ARFin normal mammary gland during pregnancy. 2) p19ARFexpression levels increased sixfold during pregnancy, and the protein level plateaus during lactation. 3) During involution, p19ARFprotein level remained at high levels at 2 and 8 days of involution and then, declined sharply at day 15. Absence of p19ARFin mammary epithelial cells leads to two major changes, 1) a delay in the early phase of involution concomitant with downregulation of p21Cip1and decrease in apoptosis, and 2) p19ARFnull cells are immortal in vivo measured by serial transplantion, which is partly attributed to complete absence of p21Cip1compared with WT cells. Although, p19ARFis dispensable in mammary alveologenesis, as evidenced by normal differentiation in the mammary gland of pregnant p19ARFnull mice, the upregulation of p19ARFby progesterone in the WT cells and the weakness of p21Cip1in mammary epithelial cells lacking p19ARFstrongly suggest that the functional role(s) of p19ARFin mammary gland development is critical to sustain normal cell proliferation rate during pregnancy and normal apoptosis in involution possibly through the p53-dependent pathway.


2000 ◽  
pp. 257-269 ◽  
Author(s):  
R Kumar ◽  
R K Vadlamudi ◽  
L Adam

Homeostasis in normal tissue is regulated by a balance between proliferative activity and cell loss by apoptosis. Apoptosis is a physiological mechanism of cell loss that depends on both pre-existing proteins and de novo protein synthesis, and the process of apoptosis is integral to normal mammary gland development and in many diseases, including breast cancer. The mammary gland is one of the few organ systems in mammals that completes its morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy that are characterized by marked alterations in breast cell proliferation and differentiation. Numerous epidemiologic studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression profiles of Bcl-2 family members. The expression of Bcl-2 family proteins in breast cancer is also influenced by estradiol and by progestin. Since the ratio of proapoptotic to antiapoptotic proteins determines apoptosis or cell survival, hormone levels may have important implications in the therapeutic prevention of breast cancer.


2019 ◽  
Vol 20 (9) ◽  
pp. 2357 ◽  
Author(s):  
Eunmi Lee ◽  
Raziye Piranlioglu ◽  
Max S. Wicha ◽  
Hasan Korkaya

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.


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