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      Transcriptome difference and potential crosstalk between liver and mammary tissue in mid-lactation primiparous dairy cows

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          Abstract

          Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative capacity in mammary tissue compared with the liver. Relatively novel is the indication by the data that the transcriptome of the liver is highly regulated by dietary and bacteria-related compounds while the mammary transcriptome is more under control of hormones, growth factors, and miRNA. A large crosstalk between the two tissues with a reciprocal control of metabolism and innate immune-adaptation was indicated by the network analysis that allowed uncovering previously unknown crosstalk between liver and mammary tissue for several signaling molecules.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Mammary gland development.

            The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.
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              Gluconeogenesis in dairy cows: the secret of making sweet milk from sour dough.

              Gluconeogenesis is a crucial process to support glucose homeostasis when nutritional supply with glucose is insufficient. Because ingested carbohydrates are efficiently fermented to short-chain fatty acids in the rumen, ruminants are required to meet the largest part of their glucose demand by de novo genesis after weaning. The qualitative difference to nonruminant species is that propionate originating from ruminal metabolism is the major substrate for gluconeogenesis. Disposal of propionate into gluconeogenesis via propionyl-CoA carboxylase, methylmalonyl-CoA mutase, and the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK) has a high metabolic priority and continues even if glucose is exogenously supplied. Gluconeogenesis is regulated at the transcriptional and several posttranscriptional levels and is under hormonal control (primarily insulin, glucagon, and growth hormone). Transcriptional regulation is relevant for regulating precursor entry into gluconeogenesis (propionate, alanine and other amino acids, lactate, and glycerol). Promoters of the bovine pyruvate carboxylase (PC) and PEPCK genes are directly controlled by metabolic products. The final steps decisive for glucose release (fructose 1,6-bisphosphatase and glucose 6-phosphatase) appear to be highly dependent on posttranscriptional regulation according to actual glucose status. Glucogenic precursor entry, together with hepatic glycogen dynamics, is mostly sufficient to meet the needs for hepatic glucose output except in high-producing dairy cows during the transition from the dry period to peak lactation. Lactating cows adapt to the increased glucose requirement for lactose production by mobilization of endogenous glucogenic substrates and increased hepatic PC expression. If these adaptations fail, lipid metabolism may be altered leading to fatty liver and ketosis. Increasing feed intake and provision of glucogenic precursors from the diet are important to ameliorate these disturbances. An improved understanding of the complex mechanisms underlying gluconeogenesis may further improve our options to enhance the postpartum health status of dairy cows. © 2010 IUBMB.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 March 2017
                2017
                : 12
                : 3
                : e0173082
                Affiliations
                [1 ]State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P.R. China
                [2 ]CAAS-ICRAF Joint Laboratory on Agroforestry and Sustainable Animal Husbandry, World Agroforestry Centre, East and Central Asia, Beijing, China
                [3 ]Synergetic Innovation Center of Food Safety and Nutrition, Harbin, China
                [4 ]Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, United States of America
                [5 ]College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu Province, P.R. China
                Wageningen UR Livestock Research, NETHERLANDS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: DB MB.

                • Data curation: MB.

                • Formal analysis: MW MB.

                • Funding acquisition: JW.

                • Investigation: LM.

                • Methodology: XN MB.

                • Software: MB.

                • Visualization: MB.

                • Writing – original draft: MB DB.

                • Writing – review & editing: MB DB.

                Article
                PONE-D-15-47560
                10.1371/journal.pone.0173082
                5349457
                28291785
                bbebe202-d0e7-4173-a1e5-0d53216b95c5
                © 2017 Bu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 November 2015
                : 15 February 2017
                Page count
                Figures: 7, Tables: 0, Pages: 24
                Funding
                Funded by: Natural Science Foundation of China
                Award ID: 313372341
                Award Recipient :
                Funded by: Ministry of Science and Technology of the People's Republic of China (CN)
                Award ID: 2012BAD12B02-5
                Award Recipient :
                Funded by: the Agriculture Science and Technology Innovation Program
                Award ID: ASTIP-IAS07
                Award Recipient :
                Funded by: USDA NEFA Multistate Project
                Award ID: NE-1048
                Award Recipient :
                This research was supported by the “Natural Science Foundation of China (31372341), the Ministry of Science and Technology of China (2012BAD12B02-5), the Agriculture Science and Technology Innovation Program (ASTIP-IAS07), and the USDA NEFA Multistate Project (NE-1048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Genetics
                Gene Types
                Regulator Genes
                Biology and Life Sciences
                Computational Biology
                Genome Analysis
                Transcriptome Analysis
                Biology and Life Sciences
                Genetics
                Genomics
                Genome Analysis
                Transcriptome Analysis
                Biology and Life Sciences
                Anatomy
                Liver
                Medicine and Health Sciences
                Anatomy
                Liver
                Biology and Life Sciences
                Genetics
                Gene Expression
                Gene Regulation
                Biology and Life Sciences
                Biochemistry
                Lipids
                Lipid Metabolism
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Lipid Metabolism
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Growth Factors
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Growth Factors
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Growth Factors
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Lactation
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Lactation
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Lactation
                Biology and Life Sciences
                Physiology
                Reproductive Physiology
                Lactation
                Medicine and Health Sciences
                Physiology
                Reproductive Physiology
                Lactation
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                All relevant data are within the paper and its Supporting Information files.

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