|Lymphocyte Development - Inserm U668|
|HEAD||Dr CUMANO Ana / firstname.lastname@example.org|
|MEMBERS||Dr BANDEIRA Antonio / BOUCOTET Laurent / BURLEN-DEFRANOUX Odile / DESANTI Guillaume / Dr GODIN Isabelle / Dr GOLUB Rachel
Dr KIEUSSEIAN Aurélie / LALANNE Ana Ines / Dr MORDELET Elodie / PEREIRA DE SOUSA Ana Patricia
Dr PEREIRA Pablo / POSSOT Cécilie / Dr VIEIRA Paulo / VOUGNY Marie-Christine
Hematopoietic cell development occurs through a succession of events involving hematopoietic stem cell generation, self-renewal, lineage commitment and differentiation. The different members of the Unit for Lymphocyte Development study in an integrative manner different aspects of hematopoietic and lymphocyte development. Hematopoietic Stem Cell generation. We have identified the site where hematopoietic stem cell generation occurs, in embryogenesis. The analysis of the environmental signals that determine the commitment of mesoderm derivatives into hematopoietic cells is crucial for the understanding of stem cell self-renewal and lineage determination. Reporter mice carrying the GFP under the control of various genes are being used to visualize hematopoietic cell generation and their interactions with the surrounding tissue.
Figure. Newly generated hematopoietic stem cells.
B-cell development. After migration to the hematopoietic organs, differentiation of hematopoietic stem cells occurs through the contact with the supporting stromal environment. Surface bound signaling molecules and cytokines determine lymphoid and myeloid lineage commitment and differentiation. We have shown that the fetal spleen environment has particular properties preventing hematopoietic stem cell renewal and favoring myeloid versus lymphoid commitment We determined that B lymphocyte production have different cytokine requirements during fetal and adult life. We showed that during hematopoietic differentiation, the common lymphoid progenitor is strictly dependent on IL-7 to maintain the B-lineage differentiation potential thus assigning an instructive role of a cytokine in lineage commitment. The roles of the IL-7, TSLP and Flt3 ligand in fetal and adult lymphocyte development are being studied in the normal and mutant mice for these cytokines.
T-cell development. In the thymus hematopoietic progenitors give rise to T lymphocytes that can be distinguished by surface marker expression and by function. Thus, T cells expressing a γδ receptor develop from the same type of precursors. We are currently investigating the rules underlying lineage commitment of γδ versus αβ expressing T cells. In the thymus, another T cell subset of regulatory T cells is generated. We have shown that neonatal thymectomy, that results in a variable degree of autoimmune disease, does not lead to an absence of regulatory T cells and therefore that they are produced in the thymus before the third day of post-natal life. The physiology and the generation of these cells that regulate homeostasis and autoimmune disease are being studied.
Keywords: Hematopoiesis, cytokines, lymphopoiesis, regulatory T cells
Dujardin, H.C., Burlen-Defranoux, O., Boucontet, L., Vieira, P., Cumano, A. & Bandeira, A. (2004) Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells. P.N.A.S. 101 : 14473-14478
Bertrand, J.Y., Giroux, S., Golub, R., Klaine, M., Jalil, A., Boucontet, L., Godin, I. & Cumano, A. (2005) Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. P.N.A.S. 102 : 134-139
Dias, S., Silva Jr, H., Cumano, A. & Vieira, P. (2005) Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors. J. Exp. Med. 201 : 971-979
Bertrand J.Y., Desanti, G.E., Lo-Man, R., Leclerc, C., Cumano, A. & Golub, R. (2006) Fetal spleen stroma drives macrophage commitment. Development 133 : 3619-3628
Cumano, A. & Godin, I. (2007) Ontogeny of the hematopoietic system. Annu. Rev. Immunol. 25 : 745-785
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