Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
Cell Prolif. 2020 Sep;53(9):e12879. doi: 10.1111/cpr.12879. Epub 2020 Aug 7.
This study aims to clarify the mechanisms underlying transcriptional regulation and regulatory roles of lncRNAs in skeletal muscle cell differentiation.
We analysed the expression patterns of lncRNAs via time-course RNA-seq. Then, we further combined the ATAC-seq and ChIP-seq to investigate the governing mechanisms of transcriptional regulation of differentially expressed (DE) lncRNAs. Weighted correlation network analysis and GO analysis were conducted to identify the transcription factor (TF)-lncRNA pairs related to skeletal muscle cell differentiation.
We identified 385 DE lncRNAs during C2C12 differentiation, the transcription of which is determined by chromatin states around their transcriptional start sites. The TF-lncRNA correlation network showed substantially concordant changes in DE lncRNAs between C2C12 differentiation and satellite cell rapid growth stages. Moreover, the up-regulated lncRNAs showed a significant decrease following the differentiation capacity of satellite cells, which gradually declines during skeletal muscle development. Notably, inhibition of the lncRNA Atcayos and Trp53cor1 led to the delayed differentiation of satellite cells. Those lncRNAs were significantly up-regulated during the rapid growth stage of satellite cells (4-6 weeks) and down-regulated with reduced differentiation capacity (8-12 weeks). It confirms that these lncRNAs are positively associated with myogenic differentiation of satellite cells during skeletal muscle development.
This study extends the understanding of mechanisms governing transcriptional regulation of lncRNAs and provides a foundation for exploring their functions in skeletal muscle cell differentiation.
本研究旨在阐明长非编码 RNA（lncRNA）在骨骼肌细胞分化中的转录调控机制和调控作用。
我们通过时间过程 RNA-seq 分析了 lncRNA 的表达模式。然后，我们进一步结合 ATAC-seq 和 ChIP-seq 来研究差异表达（DE）lncRNA 的转录调控的调控机制。进行加权相关网络分析和 GO 分析，以鉴定与骨骼肌细胞分化相关的转录因子（TF）-lncRNA 对。
我们在 C2C12 分化过程中鉴定出 385 个 DE lncRNA，其转录由其转录起始位点周围的染色质状态决定。TF-lncRNA 相关网络显示，C2C12 分化和卫星细胞快速生长阶段的 DE lncRNA 之间存在明显的一致性变化。此外，上调的 lncRNA 在卫星细胞的分化能力下降后显著下降，在骨骼肌发育过程中逐渐下降。值得注意的是，抑制 lncRNA Atcayos 和 Trp53cor1 导致卫星细胞分化延迟。这些 lncRNA 在卫星细胞的快速生长阶段（4-6 周）显著上调，而随着分化能力降低（8-12 周）下调。这证实了这些 lncRNA 与骨骼肌发育过程中卫星细胞的成肌分化呈正相关。
本研究扩展了对 lncRNA 转录调控机制的理解，并为探索它们在骨骼肌细胞分化中的功能提供了基础。
