PROJECT SUMMARY

Patients with MDS usually lack a sufficient number of circulating red cells, white cells, and platelets to meet everyday life challenges, which is due to bone marrow failure (BMF). Ineffective hematopoiesis—failure of production of hematopoietic cells at different stages of MDS cell differentiation—has long been the research focus of MDS-related BMF. In contrast, another potential reason for BMF in MDS—the impaired normal hematopoiesis, has been poorly studied. To develop new treatments that reverse BMF in MDS, we must identify mechanisms underlying the impaired normal hematopoiesis in MDS.

My present proposal aims to determine the effects of MDS on normal hematopoiesis, directly or via remodeling of the bone marrow microenvironment. We have developed approaches for imaging normal hematopoiesis in mice and generated atlases showing the differentiation of granulocytes, monocytes, dendritic cells (Zhang et al., Nature, in press), and erythrocytes. Our data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood-cell differentiation. By applying our image methods in MDS mouse models and other gene-edited mice, I hope to identify the mechanism of MDS mediated impairment of normal hematopoiesis, which will benefit the development of new effective treatment to restore normal hematopoiesis in MDS.