Researchers at the University of Wisconsin-Madison, along with colleagues at three other institutions, report the discovery of two genetic programs responsible for turning stem cells into both the red and white cells that make up human blood. The scientists say their finding is important because it identifies how nature itself makes blood products at the earliest stages of development and provides researchers with the tools to make the cells themselves, investigate how blood cells develop, and produce clinically relevant blood products.
The study (“Direct induction of hemato endothelial programs in human pluripotent stem cells by transcriptional regulators”) was reported in Nature Communications.
During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from a unique population of hemogenic endothelial cells. The new report identifies two distinct groups of transcription factors that can directly convert human stem cells into the hemogenic endothelial cells, which subsequently develop into various types of blood cells. The factors identified by Dr. Slukvin's group were capable of making the range of human blood cells including white blood cells, red blood cells, and megakaryocytes.
“We reveal two groups of transcriptional regulators capable of inducing distinct hematopoietic programs from hPSCs: pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1),” wrote the investigators. “In both cases, these transcription factors directly convert hPSCs to endothelium, which subsequently transform into blood cells with pan-myeloid or erythro-megakaryocytic potential.”
“By overexpressing just two transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo” where blood is made, added Dr. Slukvin.
An unfulfilled aspiration, according to Dr. Slukvin, is to make hematopoietic stem cells, multipotent stem cells found in bone marrow. Hematopoietic stem cells are used to treat some cancers including leukemia and multiple myeloma. Devising a method for producing them in the lab remains a significant challenge.
“We still don't know how to do that,” noted Dr. Slukvin, “but our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”