TNAP expressing adventitial pericytes contribute to myogenesis during foetal development.

Abstract

Objective: During growth and differentiation of skeletal muscle, cell types other than canonical myoblasts can be recruited to a myogenic fate. Among these, TNAP+ pericytes can differentiate into skeletal or smooth muscle cells during postnatal growth and contribute to muscle regeneration. However, their role in muscle development has not been investigated. This study aims to characterise pericyte fate choices during embryonic and foetal myogenesis, occurring in the second half of gestation.

Approach and results: Using Cre-loxP lineage tracing with multiple reporters including the multifluorescent Confetti, we labelled TNAP+ precursors in vivo and assessed the smooth or skeletal muscle differentiation in their lineage at a perinatal stage. We found that TNAP+ cells contribute in vivo to skeletal and smooth muscle cells, as well as other pericytes, also during pre-natal muscle development. The resulting clones showed that such fate choices are likely to depend on distinct unipotent progenitors rather than multipotent progenitors. In addition, we isolated and differentiated in vitro foetal cells derived from TNAP+ precursors, which showed that they are not spontaneously myogenic unless co-cultured with other skeletal muscle cells.

Conclusions: This work extends our understanding of the differentiative potency of these non- canonical skeletal muscle progenitors during prenatal life, with a view to a future application of this knowledge to optimise cell therapies for muscle wasting disorders.