Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse
- Institut Pasteur, France
- CNRS, France
Abstract
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.
Data availability
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.
Article and author information
Author details
Alexandre Grimaldi
Shahragim Tajbakhsh
Funding
Association Française contre les Myopathies (20510)
- Alexandre Grimaldi
Fondation pour la Recherche Médicale (FDT201904008277)
- Alexandre Grimaldi
Agence Nationale de la Recherche (ANR-10-LABX-73)
- Shahragim Tajbakhsh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
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).
Copyright
© 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.
Metrics
-
- 3,441
- views
-
- 482
- downloads
-
- 14
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse
eLife 11:e70235.
https://doi.org/10.7554/eLife.70235
Further reading
-
- Developmental Biology
During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
-
- Developmental Biology
- Neuroscience
The ligand Netrin mediates axon guidance through a combination of haptotaxis over short distances and chemotaxis over longer distances.
