TY - JOUR TI - Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse AU - Grimaldi, Alexandre AU - Comai, Glenda AU - Mella, Sebastien AU - Tajbakhsh, Shahragim A2 - Bronner, Marianne E A2 - Currie, Peter VL - 11 PY - 2022 DA - 2022/02/28 SP - e70235 C1 - eLife 2022;11:e70235 DO - 10.7554/eLife.70235 UR - https://doi.org/10.7554/eLife.70235 AB - 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. KW - myogenesis KW - connective tissue KW - neural crest KW - cranial mesoderm KW - scRNAseq KW - cranial muscles JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -