Inherited mutations in the X-linked hematopoietic transcription factor GATA1 lead to a wide range of blood disorders, from Diamond-Blackfan anemia to myelodysplastic syndrome. Alternative splicing produces two functionally distinct isoform of GATA1: full-length GATA1 and short GATA1 (GATA1s), which lacks the Nterminal activity-regulating module. The in vivo role of the N-terminal GATA1 domain i...

The current paradigm concerning the kinetics of hematopoiesis is that only the most primitive pluripotential bone marrow stem cells can support prolonged hematopoiesis whereas more differentiated, lineage-committed stem cells can only contribute to a particular lineage for a limited period of time. In this study, we present evidence that in mice, the spleen contains a long-lived myeloid-committ...

Signaling by vascular endothelial growth factors (VEGFs) through VEGF receptors (VEGFRs) plays important roles in vascular development and hematopoiesis. The authors analyzed the function of VEGF-C signaling through both VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis using a coculture of para-aortic splanchnopleural mesoderm (P-Sp) explants from mouse embryos with stromal cells (O...

The capacity of the yolk sac to generate multilineage, adult-type hematopoiesis was investigated in vivo using vascular endothelial-cadherin deficient embryos. In these mutants, the yolk sac is not connected to the vasculature of the embryo and therefore all hematopoietic activity detected therein is intrinsic to the yolk sac and not derived from intraembryonic sources. At embryonic days 9.5 an...

PURPOSE OF REVIEW Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking te...

Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an im...

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q- syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q-), a relatively good prognosis, and infrequent transformation to acute leukemia. The c...

Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis. The DNA-hypomethylating agents 5-azacytidine and 5-aza-2 -deoxycytidine are effective treatments for patients with MDS, increasing the time to progression to acute myelogenous leukemia and improving overall response rates. Although genome-wide increases in DNA methylation...

BACKGROUND Tyrosine kinase inhibitors, such as imatinib, are not considered curative for chronic myeloid leukemia--regardless of the significant reduction of disease burden during treatment--since they do not affect the leukemic stem cells. However, the stochastic nature of hematopoiesis and recent clinical observations suggest that this view must be revisited. DESIGN AND METHODS We studied t...

Behçet's disease (BD) is a systemic vasculitis, while myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized by ineffective hematopoiesis. Some studies suggest a relationship between MDS and BD, especially intestinal BD, and trisomy 8 seems to play an important role in both diseases. There are several reports on patients with BD comorbid with MDS i...