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Transcriptional Analysis of Fetal Mesangioblasts May Boost Muscle Regeneration Strategies

Review of “Human fetal mesoangioblasts reveal tissue-dependent transcriptional signatures” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

Mesoangioblasts, a subpopulation of pericytes or vessel‐associated stem/progenitor cells, can self‐renew and differentiate into skeletal and cardiac muscle [1]; therefore, they represent a therapeutically relevant cell source for the treatment of conditions such as muscular dystrophies or myocardial infarction. While mesoangioblasts can be readily obtained from postnatal vessels of skeletal muscle and heart of humans [2] and possess huge expansion potential during in vitro culture, their clinical application [3] suffers from problems related to poor engraftment, migration, and cell fusion efficiencies [4]. 

In a new STEM CELLS Translational Medicine article, researchers led by Marisa E. Jaconi (University of Geneva, Switzerland) sought to transcriptomically profile fetal mesoangioblasts derived from the heart, aorta, and skeletal muscle and correlate this information to their differentiation potential and therapeutic relevance [5]. Fascinatingly, the authors now associate the activity of distinct transcriptional networks in each fetal mesangioblast subtype during development to their distinct myogenic differentiation potential in a study that may help to improve mesoangioblast-based skeletal and cardiac muscle regeneration approaches.

Ronzoni et al. employed RNA sequencing to create transcriptional profiles of mesoangioblasts derived from the fetal aorta and the atrial, ventricular, and skeletal muscles, each of which displayed the ability to differentiate into adipocytes, chondrocytes, osteocytes, and smooth muscle cells in vitro. However, only skeletal mesoangioblasts produced multinucleated myotubes, while the aorta and cardiac-derived mesangioblasts all formed three-dimensional cardiac aggregates.

Analysis of the transcriptomic data established that each subset of mesoangioblasts displayed a set of differentially expressed genes, which the authors hypothesize reflect their derivation from distinct tissues. The differential mesoangioblasts transcription profiles also correlated with the inherent myogenic differentiation properties of each tissue type, while differentially expressed gene profiles demonstrated a global opposite set of upregulated and downregulated genes between skeletal muscle and cardiac mesoangioblasts, the aorta mesoangioblasts displayed an intermediate profile.

Overall, the authors provide evidence for the subtype-specific transcriptional regulation of these distinct fetal mesangioblast subtypes, which produce different muscle types, suggesting that the modulation of one part of the cardiac-specific transcriptional network in skeletal muscle-derived mesoangioblasts could allow their efficient use to repair cardiac muscle. Furthermore, the transcriptional analysis of mesangioblasts may allow the prediction of their differentiation potential, which may guide their therapeutic use without the need for any additional interventions.

For more on mesoangioblasts-based regenerative approaches to treating muscle-related conditions, stay tuned to the Stem Cells Portal!

 

References

  1. Minasi MG, Riminucci M, De Angelis L, et al., The Meso-angioblast: A Multipotent, Self-Renewing Cell that Originates from the Dorsal Aorta and Differentiates into Most Mesodermal Tissues. Development 2002;129:2773.
  2. Cossu G and Bianco P, Mesoangioblasts — Vascular Progenitors for Extravascular Mesodermal Tissues. Current Opinion in Genetics & Development 2003;13:537-542.
  3. Iyer PS, Mavoungou LO, Ronzoni F, et al., Autologous Cell Therapy Approach for Duchenne Muscular Dystrophy using PiggyBac Transposons and Mesoangioblasts. Molecular Therapy 2018;26:1093-1108.
  4. Cossu G, Previtali SC, Napolitano S, et al., Intra-arterial Transplantation of HLA-matched Donor Mesoangioblasts in Duchenne Muscular Dystrophy. EMBO Molecular Medicine 2015;7:1513-1528.
  5. Ronzoni FL, Lemeille S, Kuzyakiv R, et al., Human fetal mesoangioblasts reveal tissue-dependent transcriptional signatures. STEM CELLS Translational Medicine 2020;9:575-589.