Microenvironmental Effect on Red Cell Generation in MDS
Abstract
Anemia is the predominant clinical manifestation of MDS, especially at early stages. Erythropoiesis is a tightly regulated and complex process that requires dynamic interactions among hematopoietic stem and progenitor cells (HSPCs) with bone marrow (BM) microenvironments (also called cellular niches) to allow lineage commitment of erythroid progenitors (erythroblasts), accumulation of erythroblast, and terminal differentiation of erythroblasts to give rise to enucleated erythrocytes. The molecular pathogenesis of dysplastic erythropoiesis in MDS is largely unknown partially due to a lack of a system to study erythropoiesis in a stage-specific fashion. The goal of this project is to investigate how the intrinsic defects of erythropoiesis interact with extrinsic effects of microenvironments to result in impaired erythropoiesis in MDS. To understand the diverse mechanisms of erythroid dysplasia of MDS, we would employ our established in vitro sequential niche system to investigate the microenvironment effect on erythropoiesis and dysplastic erythropoiesis in MDS. We anticipate that diverse cellular niche cues play distinct roles in promoting the development of erythroblasts and erythroid maturation, and MDS-HSPCs either are unable to reliably communicate with niche cues or exert a forward influence on microenvironments to interfere with cellular niche function. Our designed niche system is relatively simple, based on two major stages of erythropoiesis: 1) endothelial cell (EC)niche for HSPC expansion and erythroid lineage commitment; and 2) BM stromal cell (BMSC) niche for erythroblast proliferation and maturation. In this project, we will use this niche system 1). To characterize dysplastic erythroid commitment of Low Risk-Myelodysplastic Syndromes (LR-MDS) by endothelial cell (EC) niche; 2). To examine the maturation capability of early erythroblasts derived from Myelodysplastic Syndromes (MDS) on bone marrow stromal cell (BMSC) niches.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1158167
Entities
People
- Zack Wang
Organizations
- Johns Hopkins University