Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes

TY - JOUR

T1 - Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes

AU - Buggiotti, Laura

AU - Cheng, Zhangrui

AU - Salavati, Mazdak

AU - Wathes, D. Claire

AU - GplusE Consortium

AU - Foldager, Leslie

AU - Larsen, Torben

AU - Rousing, Tine

AU - Ettema, Jehan

AU - Østergaard, Søren

AU - Sørensen, Martin Tang

AU - Ingvartsen, Klaus Lønne

PY - 2021/12

Y1 - 2021/12

N2 - 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 inlactations 2–3 (MP 2–3, n = 121), and iii) MP in lactations 4–7 (MP > 3, n = 55). Leukocyte expression was comparedbetween PP vs MP > 3 cows with MP 2–3 as background using DESeq2 followed by weighted gene co-expressionnetwork 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 thegene 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.

AB - 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 inlactations 2–3 (MP 2–3, n = 121), and iii) MP in lactations 4–7 (MP > 3, n = 55). Leukocyte expression was comparedbetween PP vs MP > 3 cows with MP 2–3 as background using DESeq2 followed by weighted gene co-expressionnetwork 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 thegene 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.

KW - Ageing

KW - Leukocytes

KW - Cow

KW - Primiparous

KW - Multiparous

KW - Longevity

UR - http://www.scopus.com/inward/record.url?scp=85115832545&partnerID=8YFLogxK

U2 - 10.1186/s12864-021-07977-5

DO - 10.1186/s12864-021-07977-5

M3 - Journal article

C2 - 34563126

SN - 1471-2164

VL - 22

SP - 1

EP - 17

JO - BMC Genomics

JF - BMC Genomics

IS - 1

M1 - 693

ER -