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Impact de l’axe de signalisation CXCL12/CXCR4 sur la spécification des cellules souches hématopoïétiques

proposé par Dr. Julia LEMOS , Inserm U1160 "EMiLy" Institut de Recherche Saint-Louis Hôpital Saint-Louis 75010 Paris

Projet de stage :

Hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) endosteal and vascular niches, serving as a reservoir for maintenance of lifelong hematopoiesis. The divergence of lymphoid and myeloid lineages occurs at the multipotent progenitor (MPP) stage and distinct subpopulations of lineage-biased MPP operate together to control blood leukocyte production. Both the localization and niches of these MPP subsets in the BM are unknown. The general objective is to delineate how the different stromal cells support MPP localization and fate in mouse BM. This will be addressed in the context of gain-of-CXCR4-function mutation which has been found to be linked to the WHIM Syndrome (WS), a rare immunodeficiency. Based on an original mouse model of WS, we recently reported defects in MPP and mesenchymal cell differentiation in BM, thus suggesting a pivotal role for CXCR4 signaling at the crossroad between both compartments. To gain further insights, deep confocal imaging on BM slices combining stroma and HSPC markers will be performed in parallel with trans-interactome analysis of these cell populations to identify ligand/receptor pairs involved in hematopoietic/stroma interactions governing MPP positioning and specification.

Techniques mises en œuvre par le stagiaire :

The student will be part of the flow cytometric- and imaging-based experiments aiming at validating the candidate genes involved in MPP/stroma crosstalk.

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