M2 - Single cell RNAseq analyses of skeletal stem cells in musculoskeletal development, growth and repair

Type de poste
Niveau d'étude minimal
Dates
Durée du poste
Contrat renouvelable
Contrat non renouvelable
Date de prise de fonction
Date de fin de validité de l'annonce
Localisation
Nom de la structure d'accueil
Adresse

INSERM U955, IMRB, Faculté de Santé de Créteil
8 rue du Général Sarrail
94000 Créteil
France

Contacts
Céline Colnot
Email du/des contacts
celine.colnot@inserm.fr
Description

Background:
Skeletal stem and progenitor cells comprise a diversity of cell populations that are essential in bone development, homeostasis and repair. These stem/progenitor cells are established during bone development and growth, and reside in several bone compartments including the bone marrow, the periosteum (the tissue at the outer surface of bone) and the growth plate. The identity of these cell populations and their role in bone repair is still elusive.
The research of the laboratory concentrates on the mechanisms of bone repair and the role of skeletal stem/progenitor cells in supporting the high regenerative capacities of bone tissues. These regenerative capacities can be compromised in trauma and diseases. Yet the cellular and molecular bases of skeletal repair dysfunctions are largely unknown limiting our ability to define appropriate treatment strategies. We have shown that during skeletal repair, stem/progenitor cells are activated within various bone compartments to participate in repair but can also be mobilized from adjacent skeletal muscle. We found that stem/progenitor cells from various origins contribute differently to the bone repair process, and are affected differently in disease and trauma. Howerer, their unique functions remain to be further elucidated. The goal of our research is to improve our understanding of the diversity of skeletal stem/progenitor cells and their biological functions.

Project:
The goal of this project is to perform large-scale transcriptome analyses of skeletal stem/progenitor cells within periosteum, bone marrow and skeletal muscle from intact tissues and after bone injury, using data generated in the laboratory and from the literature. The first aim is to define the diversity and distinct subsets of skeletal stem/progenitor cells from various tissue origins, and to define how the transcriptome profiling of cell populations change in response to bone injury. The second aim is to correlate the molecular profiling of skeletal stem/progenitor cell populations with their regenerative potential defined by functional data from the laboratory. The functional data are based on experimental results using genetic mouse models and models of impaired healing. The project will be mostly based on single cell RNA seq. analyses but will also employ classical cellular and molecular analyses for validation.
The candidate should be at ease with scripting languages (ie. R, python) and with shell usage. The candidate should have good knowledge of statistics, classification and dimension reduction methods. Previous experience in transcriptomic analysis is not mandatory but will be highly considered.

Keywords:
Skeletal Stem Cells, Bone regeneration, Cartilage, Muscle, Nervous system, Genetic mouse models, single cell omics

Recent publications from the Colnot Group:
1- Julien, A., Kanagalingam, A., Megret, J., Luka M., Menager, M., Relaix, F., Colnot, C. (2020) Direct contribution of skeletal muscle mesenchymal progenitors to bone repair. (In revision) Preprint in bioRxiv. https://doi.org/10.1101/2020.09.08.287367
2- Julien A, Perrin S, Duchamp de Lageneste O, Carvalho C, Bensidhoum M, Legeai-Mallet L and Colnot C. (2020) FGFR3 in periosteal cells drives cartilage-to-bone transformation in bone repair. Stem Cell Reports, 15, 1-13. PMID: 32916123
3- 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. PMID:29472541
4-Abou-Khalil, R, Yang, F, Lieu, S, Julien, A, Perry, J, Pereira, C, Relaix, F., Miclau, T, Marcucio, R and Colnot, C. Role of muscle stem cells during skeletal regeneration, Stem Cells, 2015, May;33(5):1501-11 PMID: 25594525
5- Abou-Khalil, R, Yang, F, Mortreux, M, Lieu, S, Yu, YY, Wurmser, M, Pereira, C, Miclau, T, Marcucio, R and Colnot, C. Delayed bone regeneration is linked to chronic inflammation in murine muscular dystrophy, Journal of Bone and Mineral Research, 2014 Feb;29(2):304-15. PMID: 23857747

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