Mots-Clés
Skeletal Stem/Progenitor Cells, Bone regeneration, cellular heterogeneity, differentiation trajectory, cellular interactions, scRNAseq, scATACseq
Description
Single-cell and multi-omics analyses of skeletal stem cells in tissue regeneration
Background: Bone regeneration is an efficient and scarless regenerative process supported by skeletal stem/progenitor cells (SSPCs) that are recruited following a bone injury to form cartilage and bone. SSPCs comprise a diversity of cell populations that are essential for healing. 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. 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. We analyze patient samples and genetic mouse models using phenotypic analyses and single cell transcriptomic analyses to elucidate the role of SSCPs in bone repair and bone diseases.
Project: The candidate will participate in current research projects in the team aiming to decipher the diverse differentiation potentials of SSPCs and how they are affected in different bone injury environments. 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. The candidate will work closely with team members involved in bioinformatic analyses and experimental research.
Qualifications:
- Knowledge of the R software and/or Python
- Knowledge of scRNAseq and scATACseq data analysis pipeline and data visualization
- Ability to develop and adapt algorithms for custom data analysis
- Knowledge in statistical analyses
- Knowledge in cellular and molecular biology is preferable
- Ability to read and communicate in English with other team members
Recent publications from the Lab:
- Perrin S, Ethel M, Bretegnier V, Goachet C, Wotawa CA, Luka M, Coulpier F, Masson C, Ménager M, Colnot C. Single nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal stem/progenitor cells in bone regeneration. Elife. 2024 Dec 6;13:RP92519. doi: 10.7554/eLife.92519.
- Hachemi Y, Perrin S, Ethel M, Julien A, Vettese J, Geisler B, Göritz C, Colnot C. Multimodal analyses of immune cells during bone repair identify macrophages as a therapeutic target in musculoskeletal trauma. Bone Research. 2024 Sep 29;12(1):56. doi: 10.1038/s41413-024-00347-3.
- Perrin S, Protic S, Bretegnier V, Laurendeau I, de Lageneste OD, Panara N, Ruckebusch O, Luka M, Masson C, Maillard T, Coulpier F, Pannier S, Wicart P, Hadj-Rabia S, Radomska KJ, Zarhrate M, Ménager M, Vidaud D, Topilko P, Parfait B, Colnot C. MEK-SHP2 inhibition prevents congenital pseudarthrosis of the tibia caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells, Sci Transl Med. 2024 Jun 26;16(753):eadj1597. doi: 10.1126/scitranslmed.adj1597. Epub 2024 Jun 26.
- Julien A, Perrin S, Martínez-Sarrà E, Kanagalingam A, Carvalho C, Luka M, Ménager M, Colnot C. Skeletal stem/progenitor cells in periosteum and skeletal muscle share a common molecular response to bone injury. J Bone Miner Res. 2022 Aug;37(8):1545-1561. doi: 10.1002/jbmr.4616. Epub 2022 Jun 29.
- Julien, A., Kanagalingam, A., Martinez-Sarra, E., Megret, J., Luka M., Menager, M., Relaix, F., Colnot, C. Direct contribution of skeletal muscle mesenchymal progenitors to bone repair. Nature Communications, 2021 May 17;12(1):2860. doi: 10.1038/s41467-021-22842-5.