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.
scRNAseq datasets are available in open access on DRYAD at the following address: https://datadryad.org/stash/dataset/doi:10.5061/dryad.gf1vhhmrs?. The code that was used to generate the driver regulators is available at this address: https://github.com/TajbakhshLab/DriverRegulators. Source data files have been provided for Figure 3J, Figure 4H, Figure 5F, Figure 5J, Figure 5-figure supplement 1E, Figure 7E and Figure 7G.
scRNAseq_raw_filtered_preprocessedDryad Digital Repository, doi:10.5061/dryad.gf1vhhmrs.
- Alexandre Grimaldi
- Alexandre Grimaldi
- Shahragim Tajbakhsh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animals were handled as per European Community guidelines and the ethics committee of the Institut Pasteur (CETEA) approved protocols (APAFIS#6354-20160809 l2028839).
- Marianne E Bronner, California Institute of Technology, United States
© 2022, Grimaldi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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