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牛科动物长肌的全转录组分析揭示了 ADAMTS6 基因在成肌细胞中的调控作用。

Whole-transcriptome analysis of longissimus dorsi muscle in cattle-yaks reveals the regulatory functions of ADAMTS6 gene in myoblasts.

机构信息

Key Laboratory of Yak Breeding Engineering Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Science, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China.

Animal Husbandry and Veterinary Workstation in Qilian County, Qilian 810400, China.

出版信息

Int J Biol Macromol. 2024 Mar;262(Pt 1):129985. doi: 10.1016/j.ijbiomac.2024.129985. Epub 2024 Feb 9.

Abstract

Cattle-yak, which is the hybrid F generation of cattle and yak, demonstrates better production performance compared to yak. However, there is limited research on the molecular mechanisms responsible for the muscle development of cattle-yak. To address this knowledge gap, a comprehensive transcriptomic survey of the longissimus dorsi muscle in cattle-yak was conducted. Three transcript types, namely lncRNAs, miRNAs, and circRNAs, along with protein-coding genes were characterized at two developmental stages (6 m, 18 m) of cattle-yak. The results revealed significant enrichment of these transcripts into pathways related to myoblast differentiation and muscle development signaling. Additionally, the study identified the TCONS00024465/circHIPK3-bta-miR-499-ADAMTS6 regulatory network, which may play a crucial role in the muscle development of cattle-yak by combining the transcriptome data of yak and constructing the ceRNA co-expression network. HEK 293 T cells were used to validate that TCONS00024465 and circHIPK3 are located upstream of bta-miR-499, and can competitively bind to bta-miR-499 as ceRNA. The study also verified that ADAMTS6 regulates skeletal muscle development by inhibiting myoblast proliferation, promoting myoblast differentiation, and positively regulating the apoptosis of myoblasts. Taken together, this study provides new insights into the advantages of cattle-yak production performance and offers a molecular basis for further research on muscle development.

摘要

犏牛是牛和牦牛的杂交 F 代,其生产性能优于牦牛。然而,对于犏牛肌肉发育的分子机制研究还很有限。为了填补这一知识空白,我们对犏牛背最长肌进行了全面的转录组学研究。在犏牛的两个发育阶段(6 月龄和 18 月龄),我们鉴定了三种转录本类型,即 lncRNA、miRNA 和 circRNA,以及蛋白质编码基因。结果表明,这些转录本显著富集到与成肌细胞分化和肌肉发育信号相关的途径中。此外,研究还发现了 TCONS00024465/circHIPK3-bta-miR-499-ADAMTS6 调控网络,该网络可能通过结合牦牛的转录组数据构建 ceRNA 共表达网络,在犏牛的肌肉发育中发挥关键作用。我们使用 HEK 293T 细胞验证了 TCONS00024465 和 circHIPK3 位于 bta-miR-499 的上游,可以作为 ceRNA 与 bta-miR-499 竞争结合。研究还验证了 ADAMTS6 通过抑制成肌细胞增殖、促进成肌细胞分化以及正向调节成肌细胞凋亡来调节骨骼肌发育。综上所述,本研究为犏牛生产性能的优势提供了新的见解,并为肌肉发育的进一步研究提供了分子基础。

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