| Přispěvatelé: |
Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ecole Doctorale Complexité du Vivant (ED515), Sorbonne Université (SU), Université Paris-Est (UPE), Freie Universität Berlin, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), We acknowledge funding support from the Institut Pasteur, Agence Nationale de la Recerche (Laboratoire d’Exellence Revive, Investissement d’Avenir, ANR-10-LABX-73 to ST and ANR-21-CE13-0005 MUSE to GC), Association Française contre les Myopathies (Grant #20510 to ST and #23201 to GC), and the Centre National de la Recherche Scientifique. M.B.D. was supported by a grant from Laboratoire d’Excellence Revive and La Ligue Contre le Cancer. We gratefully acknowledge the Genomic Patform (Inserm U1016-CNRS UMRS 8104 - Université de Paris Cité) at Institut Cochin, the UtechS Photonic BioImaging (Imagopole), C2RT, Institut Pasteur, supported by the French National Research Agency (France BioImaging, ANR-10–INSB–04, Investments for the Future) and the Center for Translational Science (CRT)-Cytometry and Biomarkers Unit of Technology and Service (CB UTechS) at Institut Pasteur for support in conducting this study., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-21-CE13-0005,MUSE,Mécanismes définissant l'hétérogénéité fonctionnelle de populations myogéniques anatomiquement distinctes(2021) |
| Popis: |
The muscle stem cell (MuSC) population is recognized as functionally heterogeneous. Cranial muscle stem cells, which originate from head mesoderm, can have greater proliferative capacity in culture and higher regenerative potential in transplantation assays when compared to those in the limb. The existence of such functional differences in phenotypic outputs remain unresolved as a comprehensive understanding of the underlying mechanisms is lacking. We addressed this issue using a combination of clonal analysis, live imaging, and scRNA-seq, identifying critical biological features that distinguish extraocular (EOM) and limb (Tibialis anterior, TA) MuSC populations. Time-lapse studies using aMyogenintdTomatoreporter showed that the increased proliferation capacity of EOM MuSCs is accompanied by a differentiation delayin vitro. Unexpectedly, in vitro activated EOM MuSCs expressed a large array of distinct extracellular matrix (ECM) components, growth factors, and signaling molecules that are typically associated with mesenchymal non-muscle cells. These unique features are regulated by a specific set of transcription factors that constitute a coregulating module. This transcription factor network, which includes Foxc1 as one of the major players, appears to be hardwired to EOM identity as it is present in quiescent adult MuSCs, in the activated counterparts during growth and retained upon passages in vitro. These findings provide insights into how high-performing MuSCs regulate myogenic commitment by active remodeling of their local environment. |
