Figure legend :

To characterize the cellular diversity of the skeletal muscle, we performed mass cytometry (CyTOF) on mononuclear cell suspensions obtained from adult mouse hindlimb muscles. Shown here is the analysis of the CyTOF dataset using the X-shift algorithm paired with single-cell force-directed layout visualization. Each cluster was annotated based on the expression of marker genes in the different major cell types. Clusters sharing the same canonical markers are depicted with the same color.

Projects

Skeletal muscle regeneration relies on the subtly orchestrated interplay between muscle stem cells and other cells that reside in or invade the wounded tissue after injury. Cell-to-cell interactions mediated by extracellular signaling cascades affect major cell functions and cause phenotypic transformations as an integral part of the response to environmental cues.

Perturbations in the architecture of this hypernetwork usually lead to defects in tissue repair. However, the environmental cues creating the transitory “regenerative” stem cell niche are poorly known.The team SPaSM assembles expertise in skeletal muscle basic cell biology and translational research to understand muscle tissue repair using an integrated multi-scale approach. We focus on signaling pathways deployed during skeletal muscle regeneration and aim to develop novel pharmacological therapies for muscular dystrophies.

Our research revolves around three aims:

i/ Using single-cell technologies, we map striated muscles cell type composition (RNA-sequencing; Mass Cytometry) during development, regeneration, ageing and in disease.

ii/ We study intracellular cytoskeleton dynamics as an endpoint of extracellular signaling pathways and decipher the cues that regulate skeletal myoblasts fusion.

iii/ We found aberrant activation of Wnt/ß-catenin and Tgfß signalings in both ageing and muscle dystrophies. We decipher the functional consequences of these mis-regulations in muscle cells.

FUNDING

• ANR Myocity (ANR-19-RAR4-0015)
• ANR Myofuge
• ANR Myofibrosis
• AFM Strat2

Selected Publications

1. Le Grand F, Jones AE, Seale V, Scimè A, Rudnicki MA. Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell.2009; 4(6) : 535-47.
2. Le Grand F, Grifone R, Mourikis P, Houbron C, Gigaud C, Pujol J, Maillet M, Pagès G, Rudnicki M, Tajbakhsh S, Maire P. Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. The Journal of Cell Biology. 2012;198(5):815-32.
3. Parisi A, Lacour F, Giordani L, Colnot S, Maire P, Le Grand F. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair. The Journal of Cell Biology.2015 Aug 31;210(5):717-26.
4. Rudolf A, Schirwis E, Giordani L, Parisi A, Lepper C, Taketo MM, Le Grand F.β-Catenin Activation in Muscle Progenitor Cells Regulates Tissue Repair. Cell Reports. 2016 May 10;15(6):1277-90.
5. Beyer S, Pontis J, Schirwis E, Battisti V, Rudolf A, Le Grand F*, Ait-Si-Ali S*. Canonical Wnt signaling regulates nuclear export of Setdb1 suring muscle terminal differentiation. Cell Discovery. 2016 Oct 17;2:16037. * equal contributions.
6. Lacour F, Vezin E, Bentzinger CF, Sincennes MC, Giordani L, Ferry A, Mitchell  R, Patel K, Rudnicki MA, Chaboissier MC, Chassot AA, Le Grand F. R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways. Cell Reports.2017 Mar 7;18(10):2320-2330.
7. Giordani, L., He, G.J., Negroni, E., Sakai, H., Law, J.Y., Siu, M.M., Wan, R., Tajbakhsh, S., Cheung, T.H., and Le Grand, F. High-dimensional single-cell cartography reveals novel skeletal muscle resident cell populations. Molecular Cell.2019 10.1016/j.molcel.2019.02.02
8. Girardi F, Taleb A, Ebrahimi M, Datye A, G. Gamage D, Peccate C, Giordani L, P. Millay D, M. Gilbert P, Cadot B & Le Grand, F. TGFβ signaling curbs cell fusion and muscle regeneration. Nat Commun 12, 750 (2021). https://doi.org/10.1038/s41467-020-20289-8
9. Le Grand, F. High-dimensional single-cell cartography reveals novel skeletal muscle resident cell populations. Molecular Cell.2019 10.1016/j.molcel.2019.02.026