title: MicroRNA deep sequencing in two adult stem cell populations identifies miR-501 as a novel regulator of myosin heavy chain during muscle regeneration.
abstract: MicroRNAs (miRNAs) are important regulators of skeletal muscle regeneration, but the underlying mechanisms are still incompletely understood. Here, comparative miRNA sequencing analysis of myogenic progenitor cells (MPs) and non-myogenic fibroblast-adipocyte progenitors (FAPs) during cardiotoxin (CTX)-induced muscle injury uncovered miR-501 as a novel muscle-specific miRNA. miR-501 is an intronic miRNA and its expression levels in MPs correlated with its host gene, chloride channel, voltage-sensitive 5 (Clcn5). Pharmacological inhibition of miR-501 dramatically blunted the induction of embryonic myosin heavy chain (MYH3) and, to a lesser extent, adult myosin isoforms during muscle regeneration, and promoted small-diameter neofibers. An unbiased target identification approach in primary myoblasts validated gigaxonin as a target of miR-501 that mimicked the effect of miR-501 inhibition on MYH3 expression. In the mdx mouse model, which models a pathological disease state, not only was miR-501 induced in regenerating skeletal muscle, but also its serum levels were increased, which correlated with the disease state of the animals. Our results suggest that miR-501 plays a key role in adult muscle regeneration and might serve as a novel serum biomarker for the activation of adult muscle stem cells.
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich 8091, Switzerland.|Competence Center Personalized Medicine UZH/ETH, ETH Zurich and University of Zurich, Zurich, Switzerland.
authors.forename: Amir
authors.initials: A
authors.lastname: Mizbani
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich 8091, Switzerland.
authors.forename: Edlira
authors.initials: E
authors.lastname: Luca
authors.affiliation: Institute of Neuropathology, University Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich 8091, Switzerland jan.kruetzfeldt@usz.ch.|Competence Center Personalized Medicine UZH/ETH, ETH Zurich and University of Zurich, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Jan
authors.identifier: 0000-0001-7071-7128
authors.initials: J
authors.lastname: Krützfeldt
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics; D012038:Regeneration / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: C000622406:MIRN501 microRNA, mouse; D035683:MicroRNAs; D018995:Myosin Heavy Chains
keywords: MicroRNA; Myosin; Regeneration; Serum; Skeletal muscle