Hematopoiesis, the dynamic process of blood cell development, is regulated by the activity of the bone morphogenetic protein (BMP) signaling pathway and by many transcription factors. However, the molecules and mechanisms that regulate BMP/Smad signaling in hematopoiesis are largely unknown. Here, we show that the Integrator complex, an evolutionarily conserved group of proteins, functions in z...

All hematopoietic and immune cells are continuously generated by hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) through highly organized process of stepwise lineage commitment. In the steady state, HSCs are mostly quiescent, while HPCs are actively proliferating and contributing to daily hematopoiesis. In response to hematopoietic challenges, e.g., life-threatening bl...

We report the scintigraphic diagnosis of thoracic extramedullary hematopoiesis in a case of alcohol-related macrocytosis. A patient with liver cirrhosis and alcohol-related macrocytosis showed multiple rounded masses in the low thoracic paraspinal region on chest radiography and CT. Whole-body scintigraphy and SPECT imaging of the thorax, after nanocolloid administration, demonstrated expansion...

During human development, hematopoiesis is thought to be compartmentalized to the fetal circulation, liver, and bone marrow. Here, we show that combinations of cytokines together with bone morphogenetic protein-4 and erythropoietin could induce multiple blood lineages from human skeletal muscle or neural tissue. Under defined serum-free conditions, the growth factors requirements, proliferation...

Myelodysplastic syndromes (MDS) are heterogeneous clonal hematologic malignancies characterized by cytopenias caused by ineffective hematopoiesis and propensity to progress to acute myeloid leukemia. Innate immunity provides immediate protection against pathogens by coordinating activation of signaling pathways in immune cells. Given the prominent role of the innate immune pathway in regulating...

We investigated hematopoiesis in untreated and ionizing radiation-exposed cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice irradiated with the dose of 4 Gy of gamma-rays and their wildtype littermates. At baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by...

Cyclic hematopoiesis is a rare disease in man in which severe neutropenia recurs at 21-day intervals with associated illness. Because lithium carbonate therapy has been shown to eliminate cyclic hematopoiesis in grey collie dogs, we examined the effects of lithium treatment on five patients with this disease. With lithium levels maintained between 0.5 and 1.0 meq/liter, these patients showed no...

Zebrafish studies in the past two decades have made major contributions to our understanding of hematopoiesis and its associated disorders. The zebrafish has proven to be a powerful organism for studies in this area owing to its amenability to large-scale genetic and chemical screening. In addition, the externally fertilized and transparent embryos allow convenient genetic manipulation and in v...

We elucidate the cellular and molecular kinetics of the stepwise differentiation of human embryonic stem cells (hESCs) to primitive and definitive erythromyelopoiesis from human embryoid bodies (hEBs) in serum-free clonogenic assays. Hematopoiesis initiates from CD45 hEB cells with emergence of semiadherent mesodermal-hematoendothelial (MHE) colonies that can generate endothelium and form organ...