Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter

HSCs are the founder cells of the adult hematopoietic system, and thus knowledge of the molecular program directing their generation during development is important for regenerative hematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus - the aorta, vitelline and umbilical arteries, yolk sac and placenta 1, 2. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters 3 and that Runx1 functions during the transition from ‘hemogenic endothelium’ to HSCs 4, 5. Here we show by conditional deletion that Runx1 activity in vascular endothelial cadherin (VEC) positive endothelial cells is indeed essential for intra-arterial cluster, hematopoietic progenitor, and HSC formation. In contrast, Runx1 is not required in cells expressing Vav, one of the first pan-hematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for hematopoietic progenitor and HSC formation from the vasculature, but its requirement ends once or before Vav is expressed

Fine-tuning of hematopoietic stem cell homeostasis: Novel role for ubiquitin ligase

Homeostasis of hematopoietic stem cells (HSCs) is a tightly regulated process, controlled by intrinsic and extrinsic signals. Although a variety of molecules involved in HSC maintenance and self-renewal are known, it remains unclear how robust HSC homeostasis is achieved. In this issue of Genes & Development, Rathinam and colleagues (pp. 992-997) report a new player in HSC homeostasis, c-Cbl ubiq-uitin ligase. They show that this E3 ubiquitin ligase acts as a negative regulator of cytokine signaling

Neonatal thrombocytosis resulting from the maternal use of non-narcotic antischizophrenic drugs during pregnancy

Neonatal thrombocytosis can result from maternal narcotic drug abuse. The case of a male infant is reported who was born to a woman with schizophrenia treated with non-narcotic psychotropic drugs during pregnancy; he developed severe prolonged thrombocytosis. The platelet count reached 1310 × 10(9)/l on day 15. This thrombocytosis persisted for three months. The patient was treated with dipyridamole. A bone marrow aspirate showed normal myeloid and erythroid precursors with an increased number of megakaryocytes. Plasma concentrations of interleukin 6 and thrombopoietin were suppressed. No obvious complications from the thrombocytosis occurred, and the platelet count fell to within the upper limit of normal after 3 months of age. This case indicates that thrombocytosis may occur in infants born to mothers treated with non-narcotic psychopharmaceutical drugs during pregnancy. The thrombocytosis in this case may have been induced by factors other than interleukin 6 or thrombopoietin.