Mots-Clés

Single cell RNA sequencing, multiomics, stem cell, tissue regeneration

Description

Laboratory: INSERM U955, Mondor Biomedical Research Institute, Univ Paris-Est Créteil, Groupe Colnot

https://colnotlab.com

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 in 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. 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. 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 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. The candidate will also participate in lab management activities including monitoring of lab stocks and mouse colonies.

Recent publications from the Lab:

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. https://www.biorxiv.org/content/10.1101/2023.06.23.546220v2
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