UC San Diego

Mature blood cells have a limited lifespan and have to be replenished continuously through a group of pluripotent precursors known as hematopoietic stem cells (HSCs). HSCs undergo proliferation and differentiation to achieve this goal. During differentiation, a group of multipotent progenitor cells with lineage-differentiation potential are generated from HSCs before becoming mature blood cells. The fate of these progenitor cells is regulated by many molecular factors during hematopoiesis. The zebrafish provides a great model to study hematopoiesis during embryonic development. Progranulin a (Grna) was found to be expressed during embryonic development by quantitative PCR (qPCR) and at the sites of hematopoiesis by whole mount in situ hybridization (WISH). Using live imaging and flow cytometry, we detected a reduction of macrophages and neutrophils in both Grna morphants and homozygous mutants. This phenotype could be partially rescued through overexpression of grna. Further analysis of grna transcripts in Pu.1 morphants suggested that Pu.1 acts upstream of Grna, regulating its expression. In addition, we found that Grna downregulated gata1 expression in Grna morphants. Together, our data suggest that Grna is essential for proper myeloid lineage differentiation.