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A CONFERENCE ORGANIZED BY THE SCIENTIFIC COUNCIL
Commitment of multipotent hematopoietic cells in the different lymphocyte lineages is poorly documented. We identified the identity of the thymic settling progenitors during embryonic development. We found that thymopoiesis is initiated by a first wave of T-lineage restricted progenitors, with limited expansion capacity but accelerated differentiation into mature T cells. Thymopoiesis is subsequently maintained by less differentiated progenitors retaining B and myeloid potential. In this second wave, starting before birth, progenitors have high proliferative but delayed differentiation capacities. To analyze the molecular events that initiate lymphoid lineage specification we identified, in fetal liver, new subsets undergoing restriction in their differentiation potential towards the T/ILC- or the B-cell lineages. Transcripts defining the molecular signatures of these two populations are sequentially up-regulated in lympho-myeloid and in common lymphoid progenitors, respectively, and precede lineage restriction indicating that T versus B-cell commitment is not a binary fate decision. We redefine the lymphoid progenitor compartment and propose a model of lineage specification in fetal liver in which the T and B transcriptional programs are primed independently at sequential developmental stages, are frequently co-expressed and are, finally, segregated in T and B biased subsets after cytokine signaling.
Contact: Carmen Buchrieser (carmen.buchrieser@pasteur.fr)