Here we see proliferating haematopoietic (blood) stem cells in which the protein FLI-1 has been introduced (dark circles with yellow border) on vascular endothelial cells (blue and red structures). Blood stem cells are used to treat various types of cancer, via cell therapy or bone marrow transplantation. To enhance the clinical success of cell therapy, it is important that the stem cells, which are normally in an inactive, dormant state, can rapidly be activated.   

Shahin Rafii of Weill Cornell Medicine (US) and colleagues have now identified FLI-1 as a crucial switch in this activation process. FLI-1 is a transcription factor involved in the regulation of thousands of genes. Absence of FLI-1 keeps stem cells in their inactive state. Once they are primed, via mRNA, to produce FLI-1, they fire into their active, regenerative state. They rapidly expand, leading to the production of new blood cells.  

Rafii’s team now wants to scale up their method to evaluate whether this approach contributes to a more robust and predictable way to stimulate blood cell production for the treatment of a variety of diseases.  

T. Itkin, et al., Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing, Nature Immunology (2025), doi:10.1038/s41590-025-02087-w