Regulation of Hematopoietic Stem Cell Aging by the Bone Marrow Niche
Age-related deterioration of hematopoietic function involves a progressive decline in the activity of blood or hematopoietic stem cells (HSCs), resulting in compromised immune responses and potentially contributing to the onset of hematologic malignancies. HSCs reside within specialized niches in the healthy bone marrow, regulating HSC proliferation and supporting their hematopoietic reconstitution potential. The mechanisms causing HSC aging have been intensely investigated in studies where the role of cell-autonomous processes has emerged. However, the precise mechanisms driving HSC niche aging have not been fully elucidated, and the specific contribution of megakaryocyte cells remains elusive. Dr. Zhang will determine how aging affects both structural and functional properties of the niche in both physiologically-aged mice and a genetic model of accelerated aging. This AFAR fellowship will help evaluate: (1) the role of the megakaryocytic niche in HSC aging, and (2) the HSC and niche rejuvenation potential of megakaryocyte-derived factors.
