Molecular Programming of blood stem and progenitor cells during vertebrate development

To maintain the blood system, billions of blood cells need to be generated on a daily basis. This is achieved by blood stem cells, immature blood cells that are able to self-renew and to generate progenitors that are committed to differentiate into mature blood cells. Blood stem cells first form from blood-forming endothelial cells in the bottom wall of the dorsal aorta in the vertebrate embryo. To learn more about the molecular programming that defines and maintains these cells we study blood-forming endothelial cells and blood stem cells in the zebrafish. We have recently performed an RNA-Seq experiment to identify genes expressed in blood-forming endothelial cells. In the course of this project, we have found several candidate genes that may play an essential role in blood stem cell formation. Making use of the latest CRISPR/Cas9 gene targeting technologies in this transparent model organism we want to knock out the candidate genes to study their roles in blood stem cell formation and maintenance. Mutant phenotypes will be studied in transgenic zebrafish lines using state-of-the-art confocal and flow cytometric analyses. Blood stem cells will be tested by an in vivo long-term blood reconstitution assay.

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