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转录组谱分析揭示 KLHL30 是成肌细胞分化的必需调节因子。

Transcriptome profile analysis reveals KLHL30 as an essential regulator for myoblast differentiation.

机构信息

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong Province, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou, 510642, China.

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, 510642, Guangdong Province, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou, 510642, China.

出版信息

Biochem Biophys Res Commun. 2021 Jun 25;559:84-91. doi: 10.1016/j.bbrc.2021.04.086. Epub 2021 Apr 29.

DOI:10.1016/j.bbrc.2021.04.086
PMID:33933993
Abstract

Skeletal muscle development is a sophisticated multistep process orchestrated by diverse myogenic transcription factors. Recent studies have suggested that Kelch-like genes play vital roles in muscle disease and myogenesis. However, it is still unclear how Kelch-like genes impact myoblast physiology. Here, through integrative analysis of the mRNA expression profile during chicken primary myoblast and C2C12 differentiation, many differentially expressed genes were found and suggested to be enriched in myoblast differentiation and muscle development. Interestingly, a little-known Kelch-like gene KLHL30 was screened as skeletal muscle-specific gene with essential roles in myogenic differentiation. Transcriptomic data and quantitative PCR analysis indicated that the expression of KLHL30 is upregulated under myoblast differentiation state. KLHL30 overexpression upregulated the protein expression of myogenic transcription factors (MYOD, MYOG, MEF2C) and induced myoblast differentiation and myotube formation, while knockdown of KLHL30 caused the opposite effect. Furthermore, KLHL30 was found to significantly decrease the numbers of cells in the S stage and thereby depress myoblast proliferation. Collectively, this study highlights that KLHL30 as a muscle-specific regulator plays essential roles in myoblast proliferation and differentiation.

摘要

骨骼肌发育是一个复杂的多步骤过程,由多种肌源性转录因子协调。最近的研究表明 Kelch 样基因在肌肉疾病和肌发生中起着至关重要的作用。然而,Kelch 样基因如何影响成肌细胞生理学仍不清楚。在这里,通过对鸡原代成肌细胞和 C2C12 分化过程中的 mRNA 表达谱进行综合分析,发现了许多差异表达的基因,并认为它们富集在成肌细胞分化和肌肉发育中。有趣的是,一个鲜为人知的 Kelch 样基因 KLHL30 被筛选为骨骼肌特异性基因,在成肌分化中具有重要作用。转录组数据和定量 PCR 分析表明,KLHL30 的表达在成肌细胞分化状态下上调。KLHL30 的过表达上调了肌源性转录因子(MYOD、MYOG、MEF2C)的蛋白表达,并诱导成肌细胞分化和肌管形成,而 KLHL30 的敲低则产生相反的效果。此外,发现 KLHL30 可显著降低 S 期细胞数量,从而抑制成肌细胞增殖。总之,这项研究强调 KLHL30 作为一种肌肉特异性调节剂,在成肌细胞增殖和分化中起着至关重要的作用。

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