scRNAseq datasets of cranial myogenic progenitors using Mesp1 and Myf5 lineages

How distinct cell fates are manifested by direct lineage ancestry from
bipotent progenitors, or by specification of individual cell types is a
key question for understanding the emergence of tissues. The interplay
between skeletal muscle progenitors and associated connective tissue cells
provides a model for examining how muscle functional units are
established. Most craniofacial structures originate from the
vertebrate-specific neural crest cells except in the dorsal portion of the
head, where they arise from cranial mesoderm. Here, using multiple
lineage-tracing strategies combined with single cell RNAseq and in situ
analyses, we identify bipotent progenitors expressing Myf5 (an upstream
regulator of myogenic fate) that give rise to both muscle and juxtaposed
connective tissue. Following this bifurcation, muscle and connective
tissue cells retain complementary signalling features and maintain spatial
proximity. Disrupting myogenic identity shifts muscle progenitors to a
connective tissue fate. The emergence of Myf5-derived connective tissue is
associated with the activity of several transcription factors, including
Foxp2. Interestingly, this unexpected bifurcation in cell fate was not
observed in craniofacial regions that are colonised by neural crest cells.
Therefore, we propose that an ancestral bi-fated program gives rise to
muscle and connective tissue cells in skeletal muscles that are deprived
of neural crest cells.