The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-free culture conditions that allow the generation of in vivo repopulating hematopoietic cells in ...

Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic...

Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS). The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA), which was synthesized from melatonin and α-lipoic acid, agains...

Hematopoietic stem progenitor cells are the source for the entire hematopoietic system. Studying gene expression in hematopoietic stem progenitor cells will provide information to understand the genetic programs controlling early hematopoiesis, and to identify the gene targets to interfere hematopoietic disorders. Extensive efforts using cell biology, molecular biology, and genomics approaches ...

Allogeneic hematopoietic stem cell transplant is safe and curative treatment modality for many hematologic diseases. Expanding alternative donor options such as haploidentical hematopoietic stem cell transplantation and umbilical cord blood, taken together with enhanced outcomes of matched unrelated donors, has resulted in a advisable donor for most patients with an hematopoietic stem cell tran...

Although the critical requirement for the transcription factor RUNX1/AML1 at the onset of hematopoietic development is well established, little is known about its transcriptional targets at this pivotal stage of blood development. Using microarrays, we identified the uncharacterized gene AI467606 as a gene whose expression level is dramatically reduced in the absence of RUNX1. We further demons...

Elucidating the in vitro differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells is important for understanding both normal and pathological hematopoietic development in vivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfully trace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monol...

DNA methylation plays an important role in the self-renewal of hematopoietic stem cells and in the commitment to the lymphoid or myeloid lineages. Using purified CD34⁺ hematopoietic progenitor cells and differentiated myeloid cell populations from the same human samples, we obtained detailed methylation profiles at distinct stages of hematopoiesis. We identified a defined set of differentiation...

Hematopoietic stem cells within the bone marrow exist in a quiescent state. They can differentiate and proliferate in response to hematopoietic stress (e.g., myelosuppression), thereby ensuring a well-regulated supply of mature and immature hematopoietic cells within the circulation. However, little is known about how this stress response is coordinated. Here, we show that plasminogen (Plg), a ...

Recent studies have established that hematopoietic stem cells (HSCs) are quiescent in homeostatic conditions but undergo extensive cell cycle and expansion upon bone marrow (BM) transplantation or hematopoietic injury. The molecular basis for HSC activation and expansion is not completely understood. In this study, we found that key developmentally critical genes controlling hematopoietic stem ...