Grant: Operating Grant

Hemopoietic stem cells (HSCs) are operationally defined as long-term repopulating, self-renewing, multipotent progenitors to all mature myeloid and lymphoid blood elements. One determinant of cell fate in the developing hemopoietic tissue are patterns of chromatinization of genomic loci that are established during differentiation, and that limit the possible outcomes of general signaling events to the activation of lineage-specific genes. We recently showed that of novel family of combinatorially assembled ATP-dependent BAF chromatin remodeling complexes plays essential roles in normal and leukemic hemopoiesis. Increasing evidence indicates that specialized BAF assemblies perform instructive and programmatic roles in the developing hemopoietic tissue by regulating the expression of lineage-specific genes. The main objective of this proposal is to define the precise developmental functions and mechanisms of action of the alternative BAF60 family of subunits in the hemopoietic system. This research program should provide a better understanding of the molecular mechanisms that pattern the hemopoietic tissue, while potentially opening new exciting avenues to the manipulation of HSC potential in regenerative medicine.