Mots-Clés

Skeletal Stem/Progenitor Cells, Bone regeneration, Cartilage, Muscle, scRNAseq, ATACseq

Description

Single-cell and multi-omics analyses of skeletal stem cells in musculoskeletal regeneration

Background: Bone regeneration is an efficient and scarless regenerative process supported by skeletal stem/progenitor cells (SSPCs) that are recruited at the site of fracture to form cartilage and bone. SSPCs comprise a diversity of cell populations that are essential in bone repair. The laboratory has shown that SSPCs reside in several bone compartments including the bone marrow and the periosteum (the tissue at the outer surface of bone), but also in adjacent skeletal muscle. We use genetic mouse models of bone repair, phenotypic analyses, and single cell transcriptomic analyses to elucidate the role of SSCPs in bone repair. Multiple differentiation events must occur for bone to heal. SSPCs respond to signals in their local tissue environment, differentiate and must self-renew. Disruption of these events can lead to delayed or failed healing.

Project: The goal of this project is to better understand the distinct differentiation potentials of SSPCs in periosteum compared to adjacent skeletal muscle and how they are affected differently in the fracture environment. We generated single cell RNA sequencing (scRNAseq) and multi-omics single cell RNA sequencing (ATACseq and RNAseq) datasets to analyze SSPC populations at steady state and after bone injury in normal and pathological conditions. The candidate will participate in scRNAseq and ATACseq analyses of SSPCs using bioinformatics tools to characterize the diversity of cell populations, their differentiation trajectory, and paracrine interactions with other cell types in their environment such as immune cells and vascular cells.

https://colnotlab.com

Recent publications from the Colnot Group:

1. Perrin S, Wotawa C-A, Luka M, Coulpier F, Masson C, Ménager M and Colnot C. Single nuclei transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration. BioRxiv, 2023 June. https://doi.org/10.1101/2023.06.23.546220
2. Julien, A., Perrin, S., Martínez‐Sarrà, E., Kanagalingam, A., Carvalho, C., Luka, M., Ménager, M., & Colnot, C. (2022). Skeletal stem/progenitor cells in periosteum and skeletal muscle share a common molecular response to bone injury. Journal of Bone and Mineral Research, 37(8), 1545-1561. https://doi.org/10.1002/jbmr.4616
3. Perrin, S., & Colnot, C. (2022). Periosteal skeletal stem and progenitor cells in bone regeneration. Current Osteoporosis Reports, 20(5), 334-343. https://doi.org/10.1007/s11914-022-00737-8
4. Julien, A., Kanagalingam, A., Martinez Sarra, E., Megret, J., Luka M., Menager, M., Relaix, F., Colnot, C. (2021). Direct contribution of skeletal muscle mesenchymal progenitors to bone repair. Nature Communications, 12(1): 2860. https://doi.org/10.1038/s41467-021-22842-5
5. Julien, A., Perrin, S., Duchamp de Lageneste, O., Carvalho, C., Bensidhoum, M., Legeai-Mallet, L., & Colnot, C. (2020). Fgfr3 in periosteal cells drives cartilage-to-bone transformation in bone repair. Stem Cell Reports, 15(4), 955-967. https://doi.org/10.1016/j.stemcr.2020.08.005
6. Duchamp de Lageneste, O, Julien, A, Abou-Khalil, R, Frangi, G, Carvalho, C, Cagnard, N, Cordier, C, Conway, SJ and Colnot, C. Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin. Nature Communications, 2018 Feb 22;9(1):773. Rai M and Duan X: F1000Prime Recommendation, 22 May 2018. DOI: 10.1038/s41467-018-03124-z