Single-cell RNA-seq analysis of Mesp1-induced skeletal myogenic development

• Published in: Biochemical and biophysical research communications 2019-12, Vol.520 (2), p.284-290
• Main Authors: Penaloza, Jacqueline S., Pappas, Matthew P., Hagen, Hannah R., Xie, Ning, Chan, Sunny S.K.
• Format: Article
• Language: English
• Subjects: Mesoderm patterning; Mesp1; Myogenic differentiation; Single-cell RNA-Sequencing; Skeletal muscle
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.09.140

The Mesp1 lineage contributes to cardiac, hematopoietic and skeletal myogenic development. Interestingly, muscle stem cells residing in craniofacial skeletal muscles primarily arise from Mesp1+ progenitors, but those in trunk and limb skeletal muscles do not. To gain insights into the difference between the head and trunk/limb muscle developmental processes, we studied Mesp1+ skeletal myogenic derivatives via single-cell RNA-seq and other strategies. Using a doxycycline-inducible Mesp1-expressing mouse embryonic stem cell line, we found that the development of Mesp1-induced skeletal myogenic progenitors can be characterized by dynamic expression of PDGFRα and VCAM1. Single-cell RNA-seq analysis further revealed the heterogeneous nature of these Mesp1+ derivatives, spanning pluripotent and mesodermal to mesenchymal and skeletal myogenic. We subsequently reconstructed the single-cell trajectories of these subpopulations. Our data thereby provide a cell fate projection of Mesp1-induced skeletal myogenesis. •Mesp1-induced skeletal myogenic progenitors express PDGFRα and VCAM1 transiently.•Single-cell RNA-seq reveals the heterogeneity of Mesp1+ derivatives.•Single-cell trajectory demonstrates Mesp1-induced skeletal myogenic development.