高海拔适应下湖羊和藏绵羊心脏组织转录组差异比较分析

doi:10.3969/j.issn.1674-7968.2026.06.007

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Abstract High-altitude hypoxic stress is a major factor affecting animal survival and physiological functions. The heart, as the central organ responsible for maintaining blood circulation and oxygen delivery in the body, directly determines an individual's ability to survive in low-oxygen environments through its energy metabolism and functional stability. This study selected the highland-adapted breed Tibetan sheep (Ovis aries) and the highland-immigrated breed Hu sheep as research subjects, differential expression genes (DEGs) in cardiac tissues were screened using high-throughput transcriptome sequencing technology and bioinformatics analysis, followed by qRT-PCR validation of the DEGs. The results showed that a total of 616 DEGs were identified in the heart tissues of 2 breeds of sheep (P<0.05). Compared with Tibetan sheep, there were 437 up-regulated genes and 179 down regulated genes in Hu sheep; Randomly selected 8 DEGs for validation, and the expression trend was consistent with the sequencing results. Further analysis revealed that key differential genes, including ATPase sarcoplasmic/endoplasmic reticulum Ca²⁺ transporting 3 (ATP2A3), natriuretic peptide B （NPPB）、phosphodiesterase 3A （PDE3A）, solute carrier family 25 member 4 （SLC25A4） and v-akt murine thymoma viral oncogene homolog 3 （AKT3）, were primarily enriched in the cGMP-PKG signaling pathway, cardiac muscle contraction, and MAPK signaling pathway. These genes might enhance the energy metabolism efficiency and functional adaptability of Hu sheep hearts under hypoxic conditions, playing a key regulatory role in hypoxia adaptation of introduced sheep. The study demonstrated that there were differences in the transcriptional levels of cardiac energy regulation genes between plateau-introduced sheep and plateau-adapted sheep. Candidate genes for hypoxia adaptation in plateau-introduced sheep, such as ATP2A3, NPPB, PDE3A, SLC25A4, and AKT3, were identified. This research provides new targets for elucidating the mechanisms of high-altitude hypoxia adaptation in sheep.

Key words： Hu sheep Tibetan sheep Heart Energy metabolism Plateau adaptation

Received: 18 September 2025

ZTFLH:

S.826.8

Corresponding Authors: *liuxiu@gsau.edu.cn

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	HE Jian-Wen
	YANG Wen-Xin
	HE Ya-Peng
	LIU Xiu

Cite this article:

HE Jian-Wen,YANG Wen-Xin,HE Ya-Peng, et al. Comparative Transcriptomic Analysis of Cardiac Tissues Between Hu Sheep and Tibetan Sheep (Ovis aries) Under High-altitude Adaptation[J]. 农业生物技术学报, 2026, 34(6): 1208-1220.

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https://journal05.magtech.org.cn/Jwk_ny/EN/10.3969/j.issn.1674-7968.2026.06.007 OR https://journal05.magtech.org.cn/Jwk_ny/EN/Y2026/V34/I6/1208

[1] 陈雪娇, 刘会杰, 臧蕾, 等. 2023. 鸡胚心脏组织转录组数据鉴定雪域白鸡高原低氧适应性关键基因[J]. 畜牧兽医学报, 54(10): 4154-4163.
(Chen X J, Liu H J, Zang L, et al.2023. Transcriptome data from chicken embryo heart tissue identified key genes for altitude hypoxia adaptation in Xueyu White chickens[J]. Acta Veterinaria et Zootechnica Sinica, 54(10): 4154-4163.)
[2] 陈杰, 何思毅. 2025. 高原心血管系统适应性改变的研究进展[J]. 心脏杂志, 3(01): 104-109.
(Chen J, He S Y.2025. Advances in adaptive changes of the cardiovascular system at high altitude[J]. Chinese Heart Journal, 37(1): 104-109.)
[3] 刘秀, 张亚强, 李少斌, 等. 2019. 藏绵羊EGLN1基因表达、变异特征及其适应性分析[J]. 华北农学报, 34(1): 226-231.
(Liu X, Zhang Y Q, Li S B, et al.2019. Analysis of EGLNl gene expression, mutation characteristics and adaptability in Tibetan sheep[J]. Acta Agriculturae Boreali-Sinica, 34(1): 226-231.)
[4] 孙国欣, 李蕴华, 赛音, 等. 2025. 湖羊群体结构分析与经济性状相关选择信号检测[J]. 畜牧兽医学报, 56(05): 2168-2181.
(Sun G X, Li Y H, Sai Y, et al.2025. Population structure analysis and economic traitsr elated selection signal detection of Hu sheep[J]. Acta Veterinaria et Zootechnica Sinica, 56(5): 2168-2181.)
[5] 田良良, 周瑞, 曹光昭, 等. 2025. 转录组测序分析黄连总碱抗脑缺血的作用机制[J]. 中国组织工程研究, 29(19):4161-4171.
(Tian L L, Zhou R, Cao G Z, et al.2025. Action mechanism of Coptidis Rhizoma alkaloids against cerebral ischemia based on transcriptome sequencing[J]. Chinese Journal of Tissue Engineering Research, 29(19):4161-4171.)
[6] 王家琦, 刘立天, 张飞飞, 等. 2022. 心力衰竭中心肌能量代谢的研究进展[J]. 河北医科大学学报, 43(8): 962-965.
(Wang J Q, Liu L T, Zhang F F, et al.2022. Research progress on myocardial energy metabolism in heart failure[J]. Journal of Hebei Medical University, 43(8): 962-965.)
[7] 王昊天, 赵瑞霞, 张天闻. 2025. 湖羊产羔性状和生长性状的分子标记研究进展[J]. 中国畜牧杂志, 61(3): 60-68.
(Wang H T, Zhao R X, Zhang T W.2025. Research progress on molecular markers of lambing and growth traits in Hu sheep[J]. Chinese Journal of Animal Science, 61(3): 60-68.)
[8] 席锐, 李发弟, 王维民, 等. 2016. 湖羊在西北寒旱地区行为学和生理指标的观测[J]. 草业学报, 25(05): 184-191.
(Xi R, Li F D, Wang W M, et al.2016. The behavoral and physiological indices of Hu sheep in the arid and cold areas of northwest China[J]. Acta Prataculturae Sinica, 25(5): 184-191.)
[9] 张瑜, 田佺, 郭亚洲, 等. 2025. 热应激条件下努比亚山羊与湖羊转录组测序的比较[J]. 饲料研究, 48(01): 150-156.
(Zhang Y, Tian Q, Guo Y Z, et al.2025. Comparison of transcriptome sequencing between Nubian goats and Hu sheep under heat stress[J]. Feed Research, 48(1): 150-156.)
[10] Anna-Lena B, Stephan S, Hannah D, et al.2022. BNIP3 regulates cardiac energy metabolism by interaction with F1FO ATP-synthase[J]. European Heart Journal, 43(2): 2896-2896.
[11] Bao Q, Zhang X, Bao P, et al.2021. Using weighted gene co-expression network analysis (WGCNA) to identify the hub genes related to hypoxic adaptation in yak (Bos grunniens)[J]. Genes Genomics, 43(10): 1231-1246.
[12] Borowiec A, Lechward K, Tkacz-Stachowska K, et al.2006. Adenosine as a metabolic regulator of tissue function: Production of adenosine by cytoplasmic 5'-nucleotidases[J]. Acta Biochimica Polonica, 53(2): 269-278.
[13] Chanda D, Luiken J J, Glatz J F.2016. Signaling pathways involved in cardiac energy metabolism[J]. FEBS Letters, 590(15): 2364-2374.
[14] Cimadamore W C, Jaiquel B S, King M. S, et al.2023. Human mitochondrial ADP/ATP carrier SLC25A4 operates with a ping-pong kinetic mechanism[J]. EMBO Reports, 24(8): e57127.
[15] Finsterer J, Zarrouk M S.2018. Phenotypic spectrum of SLC25A4 mutations[J]. Biomedical Reports,9(2): 119-122.
[16] Hanselmann R G, Welter C.2022. Origin of cancer: Cell work is the key to understanding cancer initiation and progression[J]. Frontiers in Cell and Developmental Biology, 10(1): 787995.
[17] Heinrich T.2000. Genetics of energetics: Transcriptional responses in cardiac metabolism[J]. Annals of Biomedical Engineering, 28(8): 871-876.
[18] Izaak F K, Johan S, Ryszard T S, et al.2007. Metabolic and genetic regulation of cardiac energy substrate preference[J]. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 146(1): 26-39.
[19] Javadov S, Jang S, Agostini B.2014. Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives[J]. Pharmacology & Therapeutics, 144(2): 202-225.
[20] Jerome P, Renee V C.2018. Maturation of cardiac energy metabolism during perinatal development[J]. Frontiers in Physiology, 9(10): 959.
[21] Kim Y R, Yi M, Cho S A, et al.2021. Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A)[J]. Annals of Human Genetics, 85(2): 80-91.
[22] Knight W, Yan C.2013. Therapeutic potential of PDE modulation in treating heart disease[J]. Future Medicinal Chemistry, 5(14): 1607-1620.
[23] Kolwicz S C, Purohit S, Tian R.2013. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes[J]. Circulation Research, 113(5): 603-616.
[24] Lei Y, Yang L, Zhou Y, et al.2021. Hb adaptation to hypoxia in high-altitude fishes: Fresh evidence from schizothoracinae fishes in the Qinghai-Tibetan Plateau[J]. International Journal of Biological Macromolecules, 185(3): 471-484.
[25] Li X, Wu F, Gunther S, et al.2023. Inhibition of fatty acid oxidation enables heart regeneration in adult mice[J]. Nature, 622(7983): 619-626.
[26] Martin V, Bredoux R, Corvazier E, et al.2002. Three novel sarco/endoplasmic reticulum Ca²+-ATPase (SERCA) 3 isoforms. Expression, regulation, and function of the membranes of the SERCA3 family[J]. The Journal of Biological Chemistry, 277(27): 24442-24452.
[27] Melissa H, Soraya H, Marcus K, et al.2017. Impact of cGMP-PKG pathway modulation on titin phosphorylation and titin-based myocardial passive stiffness[J]. Biophysical Journal, 112(3): 257A-257A.
[28] Mu D P, Wu X L, Feijo A, et al.2022. Transcriptome analysis of pika heart tissue reveals mechanisms underlying the adaptation of a keystone species on the roof of the world[J]. Frontiers in Genetics, 13(1): 1020789.
[29] Nakamura T, Tsujita K.2021. Current trends and future perspectives for heart failure treatment leveraging cGMP modifiers and the practical effector PKG[J]. Journal of Cardiology, 78(4): 261-268.
[30] Newton A C, Bootman M D, Scot J D.2016. Second messengers[J]. Cold Spring Harbor Perspectives in Biology, 8(8): a005926.
[31] Nolfi-Donegan D, Braganza A, Shiva S.2020. Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement[J]. Redox Biology, 37(3): 101674.
[32] Qian H, Deng T.2023. Species invasion and phylogenetic relatedness of vascular plants on the Qinghai-Tibetan Plateau, the roof of the world[J]. Plant Diversity, 01(9): 001-018.
[33] Rainer P P, Kass D A.2016. Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G[J]. Cardiovascular research,111(2): 154-162.
[34] Sara R, Kristina B K, Mathew E, et al.2021. Altered cardiac energetics and mitochondrial dysfunction in hypertrophic cardiomyopathy[J]. Circulation, 144(21): 1714-1731.
[35] Sarzani R, Allevi M, Di Pentima C, et al.2022. Role of cardiac natriuretic peptides in heart structure and function[J]. International Journal of Molecular Sciences, 23(22): 14415.
[36] Schnaitman C, Greenawalt J W.1968. Enzymatic properties of the inner and outer membranes of rat liver mitochondria[J]. The Journal of Cell Biology, 38(1): 158-175.
[37] She P, Gao B, Li D, et al.2025. The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis[J]. Nature Communications, 16(1): 232.
[38] Tsai E J, Kass D A.2009. Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics[J]. Pharmacology & Therapeutics, 122(3): 216-238.
[39] Tsyvian P B, Markhasin V S, Soloveva O E, et al.2001. Contraction-relaxation dynamics and mechanical restitution in the developing myocardium of the chick embryo[J]. Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova, 87(7): 901-910.
[40] Valdur S, Uwe S, Malgorzata T S, et al.2014. Systems level regulation of cardiac energy fluxes via metabolic cycles: Role of creatine, phosphotransfer pathways, and AMPK signaling[J]. Springer Series in Biophysics, 16(1): 261-320
[41] Wang T, Guo Y, Liu S, et al.2021. KLF4, a key regulator of a transitive triplet, acts on the TGF-beta signaling pathway and contributes to high-altitude adaptation of Tibetan pigs[J]. Frontiers in Genetics, 12: 628192.
[42] Wang Y P, Sharde A, Xu S N, et al.2021. Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis[J]. Cell Metabolism, 33(5): 1027-1041.
[43] Wen Y, Li S, Zhao F, et al.2022. Changes in the mitochondrial dynamics and functions together with the mRNA/miRNA network in the heart tissue contribute to hypoxia adaptation in Tibetan sheep[J]. Animals, 12(5): 583.
[44] Yang W, Sha Y, Chen X, et al.2024. Effects of the interaction between rumen microbiota density-VFAs-hepatic Gluconeogenesis on the adaptability of Tibetan sheep to plateau[J]. International Journal of Molecular Sciences, 25(12): 6726.
[45] Yao Y, Bade R, Li G, et al.2023. Global-scale profiling of differential expressed lysine-lactylated proteins in the cerebral endothelium of cerebral ischemia-reperfusion injury rats[J]. Cellular and Molecular Neurobiology, 43(5): 1989-2004.
[46] Zhou T, Pan J, Xu K, et al.2024. Single-cell transcriptomics in MI identify Slc25a4 as a new modulator of mitochondrial malfunction and apoptosis-associated cardiomyocyte subcluster[J]. Scientific Reports, 14(1): 9274.