Fancello I, Willett S, Castiglioni C, Amer S, Santoleri S, Bragg L, Galli F, Cossu G
Division of Cell Matrix Biology & Regenerative Medicine, FBMH, University of Manchester, UK.
Division of Cell Matrix Biology & Regenerative Medicine, FBMH, University of Manchester, UK; Institute of Experimental Neurology, Division of Neurosciences, Ospedale San Raffaele, Milan, Italy; Experimental and Clinical Research Center, Charité Medical Faculty, Max Delbrück Center Berlin, Germany.
Vascul Pharmacol. 2025 Jun;159:107489. doi: 10.1016/j.vph.2025.107489. Epub 2025 Mar 15.
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.
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.
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.
在骨骼肌生长和分化过程中，除了典型的成肌细胞外，其他细胞类型也可被诱导分化为成肌细胞。其中，TNAP+周细胞在出生后生长过程中可分化为骨骼肌或平滑肌细胞，并参与肌肉再生。然而，它们在肌肉发育中的作用尚未得到研究。本研究旨在描述妊娠后半期胚胎和胎儿成肌过程中周细胞的命运选择。
利用带有多种报告基因（包括多荧光五彩纸屑报告基因）的Cre-loxP谱系追踪技术，我们在体内标记了TNAP+前体细胞，并在围产期评估了它们谱系中的平滑肌或骨骼肌分化情况。我们发现，在产前肌肉发育过程中，TNAP+细胞在体内对骨骼肌、平滑肌细胞以及其他周细胞都有贡献。所产生的克隆表明，这种命运选择可能取决于不同的单能祖细胞而非多能祖细胞。此外，我们分离并在体外分化了源自TNAP+前体细胞的胎儿细胞，结果表明，除非与其他骨骼肌细胞共培养，它们不会自发地分化为成肌细胞。
这项工作扩展了我们对这些非典型骨骼肌祖细胞在产前分化潜能的理解，以期未来将这一知识应用于优化肌肉萎缩症的细胞治疗。
