Fishing for hemostatic proteins using comparative genomics and zebrafish models. Watkins et al compared gene expression patterns in primary human myeloid leukocytes, lymphocytes, and natural killer cells, and in model erythroblastic and megakaryocytic cells cultured from hematopoietic precursors by using whole genome chip microarray technology. Bioinformatics analysis of the resulting atlas of data identified lineage-specific genes, co-expression patterns, similarities and differences in the patterns of expressed genes in analogous murine blood cells, and genes whose protein products are candidates for new functional roles. O'Connor et al used this database to examine a subset of human platelet membrane proteins without established hemostatic functions— identified as candidates by the presence of their mRNA transcripts in megakaryocytic cells in the study by Watkins et al—for activities in experimental thrombosis. The strategy involved identification of orthologs corresponding to human platelet proteins in zebrafish cells, “knockdown” of the zebrafish orthologs using antisense morpholino oligonucleotides, and examination of responses of the morpholino-treated fish in a laser-induced thrombosis model. Reduced expression of 4 candidate proteins resulted in altered thrombus formation. Functional roles of the corresponding human proteins now merit evaluation in relevant models based on this screening strategy.

Fishing for hemostatic proteins using comparative genomics and zebrafish models. Watkins et al compared gene expression patterns in primary human myeloid leukocytes, lymphocytes, and natural killer cells, and in model erythroblastic and megakaryocytic cells cultured from hematopoietic precursors by using whole genome chip microarray technology. Bioinformatics analysis of the resulting atlas of data identified lineage-specific genes, co-expression patterns, similarities and differences in the patterns of expressed genes in analogous murine blood cells, and genes whose protein products are candidates for new functional roles. O'Connor et al used this database to examine a subset of human platelet membrane proteins without established hemostatic functions— identified as candidates by the presence of their mRNA transcripts in megakaryocytic cells in the study by Watkins et al—for activities in experimental thrombosis. The strategy involved identification of orthologs corresponding to human platelet proteins in zebrafish cells, “knockdown” of the zebrafish orthologs using antisense morpholino oligonucleotides, and examination of responses of the morpholino-treated fish in a laser-induced thrombosis model. Reduced expression of 4 candidate proteins resulted in altered thrombus formation. Functional roles of the corresponding human proteins now merit evaluation in relevant models based on this screening strategy.

Close Modal

or Create an Account

Close Modal
Close Modal