TY - JOUR
T1 - Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning
AU - Esteves de Lima, Joana
AU - Blavet, Cédrine
AU - Bonnin, Marie Ange
AU - Hirsinger, Estelle
AU - Comai, Glenda
AU - Yvernogeau, Laurent
AU - Delfini, Marie Claire
AU - Bellenger, Léa
AU - Mella, Sébastien
AU - Nassari, Sonya
AU - Robin, Catherine
AU - Schweitzer, Ronen
AU - Fournier-Thibault, Claire
AU - Jaffredo, Thierry
AU - Tajbakhsh, Shahragim
AU - Relaix, Frédéric
AU - Duprez, Delphine
N1 - Funding Information:
We thank Sophie Gournet for the illustration. We thank the Roslin Institute (Prof Helen Sang and Dr. Adrian Sherman) for providing us with GFP+ chicken eggs. The production of the GFP + chicken embryos was supported by grants from BBSRC and the Wellcome Trust. Sequencing and genome mapping of the scRNAseq datasets were performed by the GENOM’IC platform at the Cochin Institute (Paris). This work was supported by the CNRS, Inserm, SU, AFM and FRM. ARTbio was supported by the CNRS, SU, the Institut Français de Bioinformatique (IFB) and by a grant from the SIRIC CURAMUS.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while connective tissues originate from lateral plate mesoderm. With cell and genetic lineage tracing we challenge this model and identify an unexpected contribution of lateral plate-derived fibroblasts to the myogenic lineage, preferentially at the myotendinous junction. Analysis of single-cell RNA-sequencing data from whole limbs at successive developmental stages identifies a population displaying a dual muscle and connective tissue signature. BMP signalling is active in this dual population and at the tendon/muscle interface. In vivo and in vitro gain- and loss-of-function experiments show that BMP signalling regulates a fibroblast-to-myoblast conversion. These results suggest a scenario in which BMP signalling converts a subset of lateral plate mesoderm-derived cells to a myogenic fate in order to create a boundary of fibroblast-derived myonuclei at the myotendinous junction that controls limb muscle patterning.
AB - Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while connective tissues originate from lateral plate mesoderm. With cell and genetic lineage tracing we challenge this model and identify an unexpected contribution of lateral plate-derived fibroblasts to the myogenic lineage, preferentially at the myotendinous junction. Analysis of single-cell RNA-sequencing data from whole limbs at successive developmental stages identifies a population displaying a dual muscle and connective tissue signature. BMP signalling is active in this dual population and at the tendon/muscle interface. In vivo and in vitro gain- and loss-of-function experiments show that BMP signalling regulates a fibroblast-to-myoblast conversion. These results suggest a scenario in which BMP signalling converts a subset of lateral plate mesoderm-derived cells to a myogenic fate in order to create a boundary of fibroblast-derived myonuclei at the myotendinous junction that controls limb muscle patterning.
UR - https://www.scopus.com/pages/publications/85108356918
U2 - 10.1038/s41467-021-24157-x
DO - 10.1038/s41467-021-24157-x
M3 - Article
C2 - 34158501
AN - SCOPUS:85108356918
SN - 2041-1723
VL - 12
SP - 1
EP - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3851
ER -