A key repressor of blood formation

A single hematopoietic stem cell can rebuild an entire blood system, but how these cells form in the developing embryo remains a much-studied mystery. Now, a team from the Chinese Academy of Sciences has discovered a key protein that stops endothelial cells from giving rise to blood-forming cells: a finding that has potential to enable treatment of hematopoietic diseases such as Fanconi anemia or leukemia.

“Our research suggests that endothelial cells or skin fibroblasts derived from patients may be transformed into hematopoietic stem and progenitor cells at a relatively higher efficiency by inhibiting the F2r-RhoA/ROCK pathway,” says Gang Pei, from the Shanghai Institutes for Biological Sciences who led the study.

Working with mouse embryonic stem cells, Pei and his colleagues blocked the coagulation factor 2 receptor (F2R), a positive regulator of blood clotting and vascular development, and saw an increase in blood cell differentiation. Overexpressing the protein produced the opposite effect. Then using a zebrafish model they showed that F2R works through the RhoA/ROCK pathway to limit the so-called ‘endothelial-to-hematopoietic transition’ during vertebrate embryogenesis. Blocking this pathway “appears to be a potential way to efficiently generate hematopoietic stem and progenitor cells to treat blood diseases,” Pei says.