Mcleod Jonathan C, Lim Changhyun, Stokes Tanner, Sharif Jalil-Ahmad, Zeynalli Vagif, Wiens Lucas, D'Souza Alysha C, Colenso-Semple Lauren, McKendry James, Morton Robert W, Mitchell Cameron J, Oikawa Sara Y, Wahlestedt Claes, Chapple J Paul, McGlory Chris, Timmons James A, Phillips Stuart M
Department of Kinesiology, McMaster University, Hamilton, Ontario, L8S 4L8, Canada.
Population Health Sciences Institute, Faculty of Medicial Sciences, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK.
NAR Mol Med. 2024 Oct 22;1(4):ugae016. doi: 10.1093/narmme/ugae016. eCollection 2024 Oct.
A majority of human genes produce non-protein-coding RNA (ncRNA), and some have roles in development and disease. Neither ncRNA nor human skeletal muscle is ideally studied using short-read sequencing, so we used a customized RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies ( = 144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growth , while a transcriptome-driven network model demonstrated interactions via a number of discrete functional pathways and single-cell types. This analysis included established hypertrophy-related ncRNAs, including -which was leukocyte-associated (false discovery rate [FDR] = 4.9 × 10). Novel hypertrophy-linked ncRNAs included (myofibril assembly genes, FDR = 8.15 × 10), and and (vascular remodelling and angiogenesis genes, FDR = 2.77 × 10). We also discovered that hypertrophy lncRNA shows a specific myonuclear expression pattern . Our multi-layered analyses established that single-cell-associated ncRNA are identifiable from bulk muscle transcriptomic data and that hypertrophy-linked ncRNA genes mediate their association with muscle growth via multiple cell types and a set of interacting pathways.
大多数人类基因会产生非蛋白质编码RNA（ncRNA），其中一些在发育和疾病中发挥作用。使用短读长测序方法对ncRNA和人类骨骼肌进行研究都不理想，因此我们使用定制的RNA流程和网络建模，对肌肉生长过程中细胞类型特异性ncRNA反应进行大规模研究。我们完成了五项人类抗阻训练研究（n = 144名受试者），确定61%的人成功增加了肌肉量。我们生成了288个全转录组图谱，发现110个ncRNA与肌肉生长相关，而一个转录组驱动的网络模型显示，它们通过许多离散的功能途径和单细胞类型相互作用。该分析涵盖了已确定的与肥大相关的ncRNA，包括白细胞相关的ncRNA（错误发现率[FDR]=4.9×10）。与肥大相关的新ncRNA包括（肌原纤维组装基因，FDR = 8.15×10），以及和（血管重塑和血管生成基因，FDR = 2.77×10）。我们还发现，肥大lncRNA呈现出特定的肌核表达模式。我们的多层分析表明，从大块肌肉转录组数据中可识别出与单细胞相关的ncRNA，且与肥大相关的ncRNA基因通过多种细胞类型和一组相互作用的途径介导它们与肌肉生长的关联。
