The control of hematopoiesis in the human fetal liver will be investigated using the in vitro methyl cellulose culture system. Techniques of tissue culture, cell biology, immunology and membrane chemistry will be employed to answer key unsolved problems in our understanding of normal and abnormal hematopoisis.
Specific aims of these studies will be: 1) To use positive and negative selection techniques on fetal liver cells, to enrich human BFU-E, CFU-GM, and CFU-GEMM; 2) to analyze the cell interactions which control the differentiation of these hematopoietic progenitors; 3) to determine which, in any, of the cell interaction molecules known to be involved in immune interactions are found on purified hematopoietic cells. If they are present, whether these molecules act as molecular signals between hematopoietic and regulatory cells will be determined; and 4) to utilize the enriched progenitor population as an immunogen to raise antibodies to membrane determinants unique to progenitor cells. The information obtained by these studies should greatly improve our understanding of normal hematopoiesis as well as the clinical disease states of aplastic anemia, hypoplastic anemia and lymphocytosis with cytopenias.
