Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling.

Autor:	Mcleod JC; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Lim C; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.; Population Health Sciences Institute, Faculty of Medicial Sciences, Newcastle University, Newcastle upon Tyne, UK., Stokes T; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Sharif JA; Faculty of Medicine and Dentistry, Queen Mary University London, London, UK., Zeynalli V; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Wiens L; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., D'Souza AC; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Colenso-Semple L; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., McKendry J; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.; Faculty of Land and Food Systems, Food, Nutrition & Health, University of British Columbia, BC, Canada., Morton RW; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Mitchell CJ; School of Kinesiology, University of British Columbia, BC, Canada., Oikawa SY; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Wahlestedt C; University of Miami Miller School of Medicine, Miami, FL, USA., Paul Chapple J; Faculty of Medicine and Dentistry, Queen Mary University London, London, UK., McGlory C; School of Kinesiology and Health Studies, Queens University, Kingston, ON, Canada., Timmons JA; Faculty of Medicine and Dentistry, Queen Mary University London, London, UK.; University of Miami Miller School of Medicine, Miami, FL, USA., Phillips SM; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 09. Date of Electronic Publication: 2024 Oct 09.
DOI:	10.1101/2024.08.11.606848
Abstrakt:	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 customised RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies (n=144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growth in vivo, 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 CYTOR - which was leukocyte-associated (FDR = 4.9 ×10 -7 ). Novel hypertrophy-linked ncRNAs included PPP1CB-DT (myofibril assembly genes, FDR = 8.15 × 10 -8 ), and EEF1A1P24 and TMSB4XP8 (vascular remodelling and angiogenesis genes, FDR = 2.77 × 10 -5 ). We also discovered that hypertrophy lncRNA MYREM shows a specific myonuclear expression pattern in vivo . 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu