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Effects of aging on gene expression in blood of captive Tibetan macaques (Macaca thibetana) and comparisons with expression in humans

Chao-Chao Yan Xin-Shang Zhang Liang Zhou Qiao Yang Min Zhou Lin-Wan Zhang Jin-Chuan Xing Zhi-Feng Yan Megan Price Jing Li Bi-Song Yue Zhen-Xin Fan

Chao-Chao Yan, Xin-Shang Zhang, Liang Zhou, Qiao Yang, Min Zhou, Lin-Wan Zhang, Jin-Chuan Xing, Zhi-Feng Yan, Megan Price, Jing Li, Bi-Song Yue, Zhen-Xin Fan. Effects of aging on gene expression in blood of captive Tibetan macaques (Macaca thibetana) and comparisons with expression in humans. Zoological Research, 2020, 41(5): 557-563. doi: 10.24272/j.issn.2095-8137.2020.092
Citation: Chao-Chao Yan, Xin-Shang Zhang, Liang Zhou, Qiao Yang, Min Zhou, Lin-Wan Zhang, Jin-Chuan Xing, Zhi-Feng Yan, Megan Price, Jing Li, Bi-Song Yue, Zhen-Xin Fan. Effects of aging on gene expression in blood of captive Tibetan macaques (Macaca thibetana) and comparisons with expression in humans. Zoological Research, 2020, 41(5): 557-563. doi: 10.24272/j.issn.2095-8137.2020.092

衰老对圈养猕猴血液转录组的影响及其与人类的比较

doi: 10.24272/j.issn.2095-8137.2020.092

Effects of aging on gene expression in blood of captive Tibetan macaques (Macaca thibetana) and comparisons with expression in humans

Funds: This work was supported by the National Natural Science Foundation of China 31501871 (Z.X.F.), Department of Science and Technology of Sichuan Province 2019JDZH0029 (X.Z.), Department of Science and Technology of Sichuan Province 2020JDZH0026 (X.Z.), and Academy of Medical Sciences & Sichuan Provincial People’s Hospital 2017QN06 (X.Z.)
More Information
    Corresponding author: E-mail: zxfan@scu.edu.cn
  • #Authors contributed equally to this work
  • 摘要: 衰老一直是亟待解决的科学难题。藏酋猴已经作为一些人类重大疾病的动物模型,比如青光眼、糖尿病和器官移植。本文重点研究了衰老对藏酋猴血液转录组产生的影响,并且将其结果与衰老对人类血液转录组所产生的影响进行比较,比较了藏酋猴在此方面与人类的异同。我们从不同年龄的24只藏酋猴个体鉴定出1,358个显著上调差异表达基因(DEGs)和1,165个显著下调的DEGs。通过WGCNA鉴定得到两个与年龄显著相关的模块,其中的核心基因(core gene)有大部分属于DEGs。进一步分析确定出藏酋猴应对衰老的潜在重要通路,FoxO signaling pathway和B cell receptor signaling pathway。在藏酋猴和人类的对比分析中,鉴定出279个藏酋猴与人类共享的年龄相关DEGs,其中27个在两个物种的表达不同。例如在B cell receptor signaling pathway中起着激活B细胞下游体液免疫的INPPL1基因,在人类中随年龄增长表达量上调,但在藏酋猴中随年龄增长表达量下调。本文对年龄在藏酋猴血液组织基因表达中的作用进行了研究,发现了藏酋猴与人类在重要调控通路中表达模式异同的基因,为藏酋猴未来更好地充当疾病模式动物提供了参考。
    #Authors contributed equally to this work
  • Figure  1.  Gene expression changes in different Tibetan macaques (TMs)

    A: Assessment of effects of variables on gene expression. Distribution of each sample in top two principal components. Color of dots indicates age, with cooler tones indicating younger individuals. F: Female; M: Male. B: Relationship between TM traits and modules identified by WGCNA. C: B cell receptor signaling pathway (mcc04662). Up-regulated DEGs with age are marked in purple, down-regulated DEGs with age are marked in light blue. Activation process is shown with red arrow, indirect activation process is shown with dotted arrow. D: FoxO signaling pathway (mcc04068). Expression of up-regulated DEGs with age in TMs are marked in purple (upstream of main pathway) and light brown (downstream of main pathway), down-regulated DEGs with age are marked in light blue. Activation process is shown with red arrow, indirect activation process is shown with dotted arrow.

    Table  1.   Age-related DEGs in Tibetan macaques with opposite expression to humans

    Gene namelog2FCP-valueGene description
    NET10.1004022.30E–05Neuroepithelial cell transforming 1
    MAML20.0644290.000227Mastermind like transcriptional coactivator 2
    TBC1D40.0539050.000237TBC1 domain family, member 4
    LPGAT10.0739520.000393Lysophosphatidylglycerol acyltransferase 1
    CEP1350.0832350.00043Centrosomal protein 135
    TGFBR20.0509340.000482TGF-beta receptor type-2 precursor
    LARP40.0464320.001619La ribonucleoprotein domain family member 4
    NIN0.0595290.001998Ninein
    RORC0.0659320.002403RAR related orphan receptor C
    RNF144A0.0378140.005089Ring finger protein 144A
    PGRMC20.0238640.006044Progesterone receptor membrane component 2
    TIGD70.0405310.006794Tigger transposable element derived 7
    CRLF30.0306610.006891Cytokine receptor like factor 3
    FNIP10.0446190.007115FNIP1
    PDE3B0.0348510.007153Phosphodiesterase 3B
    OSBPL5–0.104691.58E–08Oxysterol binding protein like 5
    CDKN1C–0.151785.59E–05Cyclin dependent kinase inhibitor 1C
    IL18BP–0.047660.00071Interleukin 18 binding protein
    PALLD–0.098380.000947Palladin, cytoskeletal associated protein
    EPB41L4A–0.087940.001517Erythrocyte membrane protein band 4.1 like 4A
    INPPL1–0.033250.002177Inositol polyphosphate phosphatase like 1
    IL12RB1–0.056670.002345Interleukin 12 receptor subunit beta 1
    TIMP1–0.114890.003691Metalloproteinase inhibitor 1
    GNLY–0.075130.004472Granulysin
    FAM46A–0.022720.005602Family with sequence similarity 46 member A
    TAGLN–0.071850.008341Transgelin
    AGPAT4–0.043140.008351-acylglycerol-3-phosphate O-acyltransferase 4
    下载: 导出CSV
  • [1] Anders S, Pyl PT, Huber W. 2015. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics, 31(2): 166−169. doi:  10.1093/bioinformatics/btu638
    [2] Aziz H, Zaas A, Ginsburg GS. 2007. Peripheral blood gene expression profiling for cardiovascular disease assessment. Genomic Medicine, 1(3-4): 105−112. doi:  10.1007/s11568-008-9017-x
    [3] Charruau P, Johnston RA, Stahler DR, Lea A, Snyder-Mackler N, Smith DW, et al. 2016. Pervasive effects of aging on gene expression in wild wolves. Molecular Biology and Evolution, 33(8): 1967−1978. doi:  10.1093/molbev/msw072
    [4] Dannemann M, Kelso J. 2017. The contribution of Neanderthals to phenotypic variation in modern humans. The American Journal of Human Genetics, 101(4): 578−589. doi:  10.1016/j.ajhg.2017.09.010
    [5] de Magalhães JP, Passos JF. 2018. Stress, cell senescence and organismal ageing. Mechanisms of Ageing and Development, 170: 2−9. doi:  10.1016/j.mad.2017.07.001
    [6] Eghlidi DH, Luna SL, Brown DI, Garyfallou VT, Kohama SG, Urbanski HF. 2018. Gene expression profiling of the SCN in young and old rhesus macaques. Journal of Molecular Endocrinology, 61(2): 57−67. doi:  10.1530/JME-18-0062
    [7] Fan ZX, Zhao G, Li P, Osada N, Xing JC, Yi Y, et al. 2014. Whole-genome sequencing of Tibetan macaque (Macaca thibetana) provides new insight into the macaque evolutionary history. Molecular Biology and Evolution, 31(6): 1475−1489. doi:  10.1093/molbev/msu104
    [8] Favaloro EJ, Franchini M, Lippi G. 2014. Aging hemostasis: changes to laboratory markers of hemostasis as we age-a narrative review. Seminars in Thrombosis and Hemostasis, 40(6): 621−633. doi:  10.1055/s-0034-1384631
    [9] Frehlick LJ, Eirín-López JM, Ausió J. 2007. New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones. BioEssays, 29(1): 49−59. doi:  10.1002/bies.20512
    [10] Gibbons A. 2017. Neandertal genome reveals greater legacy in the living. Science, 358(6359): 21. doi:  10.1126/science.358.6359.21
    [11] Göring HHH, Curran JE, Johnson MP, Dyer TD, Charlesworth J, Cole SA, et al. 2007. Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nature Genetics, 39(10): 1208−1216. doi:  10.1038/ng2119
    [12] Granneman S, Tollervey D. 2007. Building ribosomes: even more expensive than expected?. Current Biology, 17(11): R415−R417. doi:  10.1016/j.cub.2007.04.011
    [13] Hong MG, Myers AJ, Magnusson PKE, Prince JA. 2008. Transcriptome-wide assessment of human brain and lymphocyte senescence. PLoS One, 3(8): e3024. doi:  10.1371/journal.pone.0003024
    [14] Hoopes BC, Rimbault M, Liebers D, Ostrander EA, Sutter NB. 2012. The insulin-like growth factor 1 receptor (IGF1R) contributes to reduced size in dogs. Mammalian Genome, 23(11-12): 780−790. doi:  10.1007/s00335-012-9417-z
    [15] Horvath S, Zhang YF, Langfelder P, Kahn RS, Boks MPM, van Eijk K, et al. 2012. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biology, 13(10): R97. doi:  10.1186/gb-2012-13-10-r97
    [16] Kenyon CJ. 2010. The genetics of ageing. Nature, 467(7315): 622.
    [17] Kim D, Langmead B, Salzberg SL. 2015. HISAT: a fast spliced aligner with low memory requirements. Nature Methods, 12(4): 357−360. doi:  10.1038/nmeth.3317
    [18] Lan Y, Wang J, Yang Q, Tang RX, Zhou M, Lei GL, et al. 2020. Blood transcriptome analysis reveals gene expression features of breast-feeding rhesus macaque (Macaca mulatta) infants. Zoological Research, 41(4): 431−436. doi:  10.24272/j.issn.2095-8137.2020.044
    [19] Lapointe J, Li CD, Higgins JP, van de Rijn M, Bair E, Montgomery K, et al. 2004. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 101(3): 811−816. doi:  10.1073/pnas.0304146101
    [20] Lindqvist LM, Tandoc K, Topisirovic I, Furic L. 2018. Cross-talk between protein synthesis, energy metabolism and autophagy in cancer. Current Opinion in Genetics & Development, 48: 104−111.
    [21] López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. 2013. The hallmarks of aging. Cell, 153(6): 1194−1217. doi:  10.1016/j.cell.2013.05.039
    [22] Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15(12): 550. doi:  10.1186/s13059-014-0550-8
    [23] Lyman GH, Culakova E, Poniewierski MS, Kuderer NM. 2018. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. Thrombosis Research, 164: S112−S118. doi:  10.1016/j.thromres.2018.01.028
    [24] Mari D, Coppola R, Provenzano R. 2008. Hemostasis factors and aging. Experimental Gerontology, 43(2): 66−73. doi:  10.1016/j.exger.2007.06.014
    [25] Mesko B, Poliska S, Nagy L. 2011. Gene expression profiles in peripheral blood for the diagnosis of autoimmune diseases. Trends in Molecular Medicine, 17(4): 223−33. doi:  10.1016/j.molmed.2010.12.004
    [26] Peters MJ, Joehanes R, Pilling LC, Schurmann C, Conneely KN, Powell J, et al. 2015. The transcriptional landscape of age in human peripheral blood. Nature Communications, 6: 8570. doi:  10.1038/ncomms9570
    [27] Reynolds LM, Ding JZ, Taylor JR, Lohman K, Soranzo N, de la Fuente A, et al. 2015. Transcriptomic profiles of aging in purified human immune cells. BMC Genomics, 16(1): 333. doi:  10.1186/s12864-015-1522-4
    [28] Sheffield WD, Squire RA, Strandberg JD. 1981. Cerebral venous thrombosis in the rhesus monkey. Veterinary Pathology, 18(3): 326−334. doi:  10.1177/030098588101800305
    [29] Shu TJ, Zhang YZ. 2007. Nucleoplasmin, an important nuclear chaperone. Chinese Journal of Biochemistry and Molecular Biology, 23(9): 718−723. (in Chinese)
    [30] Simon AK, Hollander GA, McMichael A. 2015. Evolution of the immune system in humans from infancy to old age. Proceedings Biological Sciences, 282(1821): 20143085.
    [31] Stute P, Sielker S, Wood CE, Register TC, Lees CJ, Dewi FN, Williams JK, Wagner JD, Stefenelli U, Cline JM. 2012. Life stage differences in mammary gland gene expression profile in non-human primates. Breast Cancer Research and Treatment, 133(2): 617−634.
    [32] Tung J, Zhou X, Alberts SC, Stephens M, Gilad Y. 2015. The genetic architecture of gene expression levels in wild baboons. eLife, 4: e04729. doi:  10.7554/eLife.04729
    [33] van der Horst A, Burgering BMT. 2007. Stressing the role of foxo proteins in lifespan and disease. Nature Reviews Molecular Cell Biology, 8(6): 440−450. doi:  10.1038/nrm2190
    [34] van den Akker EB, Passtoors WM, Jansen R, van Zwet EW, Goeman JJ, Hulsman M, et al. 2014. Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein- protein interaction modules as robust markers of human aging. Aging Cell, 13(2): 216−225. doi:  10.1111/acel.12160
    [35] Wei K, Liang X, Zou FD, Yin HL, Yue BS. 2006. Molecular cloning and sequence analysis of interferon-gamma and interleukin-6 from Tibetan macaque (Macaca thibetana). Veterinary Immunology and Immunopathology, 114(3−4): 346−354. doi:  10.1016/j.vetimm.2006.08.014
    [36] Wu D, Yi Y, Sun F, Zhou L, Yang F, Wang H, et al. 2014. Effects of age and sex on the hematology and blood chemistry of Tibetan macaques (Macaca thibetana). Journal of the American Association for Laboratory Animal Science, 53(1): 12−17.
    [37] Wu D, Yue F, Zou CL, Chan P, Zhang YA. 2012. Analysis of glucose metabolism in cynomolgus monkeys during aging. Biogerontology, 13(2): 147−155. doi:  10.1007/s10522-011-9364-1
    [38] Xie C, Mao XZ, Huang JJ, Ding Y, Wu JM, Dong S, et al. 2011. KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Research, 39(S2): W316−W322.
    [39] Yao YF, Zhao JJ, Dai QX, Li JY, Zhou L, Wang YT, et al. 2013. Identification and characterization of the major histocompatibility complex class II DQB (MhcMath-DQB1) alleles in Tibetan macaques (Macaca thibetana). Tissue Antigens, 82(2): 113−121. doi:  10.1111/tan.12145
    [40] Yin JA, Gao G, Liu XJ, Hao ZQ, Li K, Kang XL, et al. 2017. Genetic variation in glia-neuron signalling modulates ageing rate. Nature, 551(7679): 198−203. doi:  10.1038/nature24463
    [41] Zheng HR, Liu T, Lei TT, Girani L, Wang Y, Deng SP. 2019. Promising potentials of Tibetan macaques in xenotransplantation. Xenotransplantation, 26(1): e12489. doi:  10.1111/xen.12489
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  • 收稿日期:  2020-04-23
  • 录用日期:  2020-06-18
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