A recessive screen for genes regulating hematopoietic stem cells. Blood. 2010 Jul 7; Authors: Papathanasiou P, Tunningley R, Pattabiraman DR, Ye P, Gonda TJ, Whittle B, Hamilton AE, Cridland SO, Lourie R, Perkins AC Identification of genes that regulate the development, self-renewal and differentiation of stem cells is of vital importance for understanding normal organogenesis and cancer; such knowledge also underpins regenerative medicine. Here we demonstrate that chemical mutagenesis of mice combined with advances in hematopoietic stem cell reagents and genome resources can efficiently recover recessive mutations and identify genes essential for generation and proliferation of definitive hematopoietic stem cells and/or their progeny. We employed high-throughput FACS to analyze nine subsets of blood stem cells, progenitor cells, circulating red cells and platelets in >1,300 mouse embryos at embryonic day (E) 14.5. From 45 pedigrees we recovered six strains with defects in definitive hematopoiesis. We demonstrate rapid identification of a novel mutation in the c-Myb transcription factor that results in thrombocythemia and myelofibrosis as proof-of-principal of the utility of our FACS-based screen. Such phenotype-driven approaches will provide new knowledge of genes, protein interactions and regulatory networks which underpin stem cell biology. PMID: 20610815 [PubMed - as supplied by publisher] | 
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