Human fetal mesoangioblasts reveal tissue-dependent transcriptional signatures

Abstract

Abstract Mesoangioblasts (MABs) derived from adult skeletal muscles are well-studied adult stem/progenitor cells that already entered clinical trials for muscle regeneration in genetic diseases; however, the transcriptional identity of human fetal MABs (fMABs) remains largely unknown. Herein we analyzed the transcriptome of MABs isolated according to canonical markers from fetal atrium, ventricle, aorta, and skeletal muscles (from 9.5 to 13 weeks of age) to uncover specific gene signatures correlating with their peculiar myogenic differentiation properties inherent to their tissue of origin. RNA-seq analysis revealed for the first time that human MABs from fetal aorta, cardiac (atrial and ventricular), and skeletal muscles display subsets of differentially expressed genes likely representing distinct expression signatures indicative of their original tissue. Identified GO biological processes and KEGG pathways likely account for their distinct differentiation outcomes and provide a set of critical genes possibly predicting future specific differentiation outcomes. This study reveals novel information regarding the potential of human fMABs that may help to improve specific differentiation outcomes relevant for therapeutic muscle regeneration. Significance statement The current study reveals transcriptional identities in human fetal mesoangioblasts (fMABs) from aorta, cardiac, and skeletal muscle tissues, with specific gene signatures correlating with their peculiar myogenic differentiation properties inherent to their derivative tissues. Gene network analysis identified four major superclusters of differentially expressed genes and uncovered a global opposite set of upregulated and downregulated genes between skeletal and cardiac muscle MABs, with the ones from aorta showing an intermediate profile. Collectively, the current work provides a set of critical genes accounting of, and possibly predicting, lineage-specific differentiation commitments during development. This knowledge may help improve the future management of muscle regeneration.