Abstract:
Improving livestock and poultry growth rates and increasing meat production are urgently needed worldwide. Previously, we produced a myostatin (MSTN) and fibroblast growth factor 5 (FGF5) double-knockout (MF-/-) sheep by CRISPR Cas9 system to improve meat production, and also wool production. Both MF-/- sheep and the F1 generation (MF+/-) sheep showed an obvious \"double-muscle\" phenotype. In this study, we identified the expression profiles of long noncoding RNAs (lncRNAs) in wild-type and MF+/- sheep, then screened out the key candidate lncRNAs that can regulate myogenic differentiation and skeletal muscle development. These key candidate lncRNAs can serve as critical gatekeepers for muscle contraction, calcium ion transport and skeletal muscle cell differentiation, apoptosis, autophagy, and skeletal muscle inflammation, further revealing that lncRNAs play crucial roles in regulating muscle phenotype in MF+/- sheep. In conclusion, our newly identified lncRNAs may emerge as novel molecules for muscle development or muscle disease and provide a new reference for MSTN-mediated regulation of skeletal muscle development.
摘要:
全世界迫切需要提高牲畜和家禽的生长速度和增加肉类产量。以前,我们通过CRISPRCas9系统生产了肌肉生长抑制素(MSTN)和成纤维细胞生长因子5(FGF5)双敲除(MF-/-)绵羊,以提高肉类产量,还有羊毛生产。MF-/-绵羊和F1代(MF/-)绵羊均表现出明显的“双肌”表型。在这项研究中,我们确定了野生型和MF+/-绵羊的长链非编码RNA(lncRNAs)的表达谱,然后筛选出能够调控成肌分化和骨骼肌发育的关键候选lncRNAs。这些关键的候选lncRNAs可以作为肌肉收缩的关键看门人,钙离子转运与骨骼肌细胞分化,凋亡,自噬,和骨骼肌炎症,进一步揭示lncRNAs在调节MF+/-绵羊的肌肉表型中起关键作用。总之,我们新鉴定的lncRNAs可能作为肌肉发育或肌肉疾病的新分子出现,并为MSTN介导的骨骼肌发育调控提供新的参考。