Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes
Laura Buggiotti, Zhangrui Cheng, Mazdak Salavati, Claire Wathes, Alan G. Fahey, Alessandra Crisà, Ali Fouladi, A.R.G. Wylie, Amélie Vanlierde, Anders Fogh, Andreia Santoro, A.R. Cromie, Anne-Sophie Van Laere, Armin Pearn, Arnold Evertson, Aurélie Laine, Beatriz Sanz‐Bernardo, B. Moioli, Bonny Vanranst, Catherine Bastin, Charlotte Gaillard, Tan Chen, Chris Elsik, Cinzia Marchitelli, Claire Wathes, Clément Grelet, C.J. Byrne, C.P. Ferris, Daragh Matthews, Deborah A. Triant, Dirk Werling, Elizabeth Matthews, Else Meyer, Éric Froidmont, Federica Signorelli, Fiona Carter, F. Napolitano, F. Kearney, Frank Becker, Frédéric Colinet, Frédéric Dehareng, Gavin C. Conant, Geert Opsomer, Geoff Pollott, Guiqiang Wang, Guohua Hua, Hannes Bogaert, Haruko Takeda, Hedi Hammami, Huanchun Chen, Jan Vandepitte, Janne Rothmann, Jehan Frans Ettema, Jenne De Koster, Jennifer C. McClure, Jerry W. Taylor, Johanna Höglund, Junlong Zhao, K.L. Ingvartsen, Kristof Hermans, Leila Vandevelde, Leslie Foldager, Liguo Yang, Linda Kosten, L. Buttazzoni, Marilou Ramos Pamplona, M.A. Crowe, Marlene Sciarretta, Martin Schulze, Martin Tang Sørensen, Matthew R. Bell, Matt McClure, M.C. Lucy, Mazdak Salavati, M. Bonneau, Michel Georges, Mieke Vaneetvelde, Miel Hostens, Mogens Agerbo Krogh, Niamh McLoughlin, Nicolas Gengler, Pauline M. Rudd, Rodrigo Reis Mota, Róisín O’Flaherty, Saied Naderi Darbagshahi, Sander Moerman, Sham Vera, Shujun Zhang, Sinead Hallinan, Søren Østergaard, Susanne Dahl, Thomas Andersen, Tine Rousing, Torben Larsen, Victor Henrique Silva de Oliveira, Xing Chen, Zhangrui Cheng
Abstract
BACKGROUND: Previous studies have identified many immune pathways which are consistently altered in humans and model organisms as they age. Dairy cows are often culled at quite young ages due to an inability to cope adequately with metabolic and infectious diseases, resulting in reduced milk production and infertility. Improved longevity is therefore a desirable trait which would benefit both farmers and their cows. This study analysed the transcriptome derived from RNA-seq data of leukocytes obtained from Holstein cows in early lactation with respect to lactation number. RESULTS: Samples were divided into three lactation groups for analysis: i) primiparous (PP, n = 53), ii) multiparous in lactations 2-3 (MP 2-3, n = 121), and iii) MP in lactations 4-7 (MP > 3, n = 55). Leukocyte expression was compared between PP vs MP > 3 cows with MP 2-3 as background using DESeq2 followed by weighted gene co-expression network analysis (WGCNA). Seven modules were significantly correlated (r ≥ 0.25) to the trait lactation number. Genes from the modules which were more highly expressed in either the PP or MP > 3 cows were pooled, and the gene lists subjected to David functional annotation cluster analysis. The top three clusters from modules more highly expressed in the PP cows all involved regulation of gene transcription, particularly zinc fingers. Another cluster included genes encoding enzymes in the mitochondrial beta-oxidation pathway. Top clusters up-regulated in MP > 3 cows included the terms Glycolysis/Gluconeogenesis, C-type lectin, and Immunity. Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function (CCR7, CD27, IL7R, CAMK4, CD28), mitochondrial ribosomal proteins (MRPS27, MRPS9, MRPS31), and DNA replication and repair (WRN). Those up-regulated in MP > 3 cows encoded immune defence proteins (LYZ, CTSZ, SREBF1, GRN, ANXA5, ADARB1). CONCLUSIONS: Genes and pathways associated with lactation number in cows were identified for the first time to date, and we found that many were comparable to those known to be associated with ageing in humans and model organisms. We also detected changes in energy utilization and immune responses in leukocytes from older cows.