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BBB seminar: Mikael Sigvardsson

Unraveling genetic networks in B-lymphocyte lineage commitment

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Mikael Sigvardsson
Department of Stem Cell Biology, Lund University, Sweden

The development of B lineage cells from multipotent hematopoietic stem cells involves a series of stages where the lineage potential of the progenitor cells is gradually lost. In order to increase the understanding of how the B-lineage pathway is initiated, we have performed gene expression analysis and functional investigations of cells proceeding through development. These experiments suggest that lymphoid priming is initiated before the complete loss of myeloid developmental potential but that true commitment is not achieved until the late CLP (common lymphoid progenitor) stage. The lymphoid priming primarily involves genes expressed in both B and T lineage cells while the expression of B/T restricted genes is initiated at a later stage of development. In order to investigate the integration of extra-cellular signals and the ongoing genetic program, we have also developed a database for gene expression based receptor/ligand analyses. This has allowed us to identify novel possibilities for stage specific communication between the developing B-cell and the surrounding stroma cells.