Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning

Joana Esteves de Lima; Cédrine Blavet; Marie-Ange Bonnin; Estelle Hirsinger; Glenda Comai; Laurent Yvernogeau; Marie-Claire Delfini; Léa Bellenger; Sébastien Mella; Sonya Nassari; Catherine Robin; Ronen Schweitzer; Claire Fournier-Thibault; Thierry Jaffredo; Shahragim Tajbakhsh; Frédéric Relaix; Delphine Duprez

doi:10.1038/s41467-021-24157-x

Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning

Joana Esteves de Lima, Cédrine Blavet, Marie-Ange Bonnin, Estelle Hirsinger, Glenda Comai, Laurent Yvernogeau, Marie-Claire Delfini, Léa Bellenger, Sébastien Mella, Sonya Nassari, Catherine Robin, Ronen Schweitzer, Claire Fournier-Thibault, Thierry Jaffredo, Shahragim Tajbakhsh, Frédéric Relaix, Delphine Duprez

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

29 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	3851
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-24157-x
Publication status	Published - 22 Jun 2021

Keywords

Animals
Body Patterning/genetics
Cell Lineage/genetics
Cells, Cultured
Chick Embryo
Extremities/embryology
Fibroblasts/cytology
Gene Expression Regulation, Developmental
Mesoderm/cytology
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Muscle Development/genetics
Muscle, Skeletal/cytology
Reverse Transcriptase Polymerase Chain Reaction
Somites/cytology

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Esteves de Lima, J., Blavet, C., Bonnin, M.-A., Hirsinger, E., Comai, G., Yvernogeau, L., Delfini, M.-C., Bellenger, L., Mella, S., Nassari, S., Robin, C., Schweitzer, R., Fournier-Thibault, C., Jaffredo, T., Tajbakhsh, S., Relaix, F., & Duprez, D. (2021). Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning. Nature Communications, 12(1), 3851. https://doi.org/10.1038/s41467-021-24157-x

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abstract = "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.",

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doi = "10.1038/s41467-021-24157-x",

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Esteves de Lima, J, Blavet, C, Bonnin, M-A, Hirsinger, E, Comai, G, Yvernogeau, L, Delfini, M-C, Bellenger, L, Mella, S, Nassari, S, Robin, C, Schweitzer, R, Fournier-Thibault, C, Jaffredo, T, Tajbakhsh, S, Relaix, F & Duprez, D 2021, 'Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning', Nature Communications, vol. 12, no. 1, pp. 3851. https://doi.org/10.1038/s41467-021-24157-x

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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

PY - 2021/6/22

Y1 - 2021/6/22

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.

KW - Animals

KW - Body Patterning/genetics

KW - Cell Lineage/genetics

KW - Cells, Cultured

KW - Chick Embryo

KW - Extremities/embryology

KW - Fibroblasts/cytology

KW - Gene Expression Regulation, Developmental

KW - Mesoderm/cytology

KW - Mice, Inbred C57BL

KW - Mice, Inbred DBA

KW - Mice, Transgenic

KW - Muscle Development/genetics

KW - Muscle, Skeletal/cytology

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Somites/cytology

U2 - 10.1038/s41467-021-24157-x

DO - 10.1038/s41467-021-24157-x

M3 - Article

C2 - 34158501

SN - 2041-1723

VL - 12

SP - 3851

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning

Abstract

Keywords

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