A GROUNDBREAKING study has revealed new insights into the molecular mechanisms that govern the activation and quiescence of haematopoietic stem and progenitor cells (HSPCs). These cells are essential for blood production and immune function, but understanding their regulation has long remained elusive. Researchers discovered that the Fli-1 transcription factor plays a critical role in the activation of HSPCs during regenerative haematopoiesis, the process by which blood cells are replenished after injury.
The study, conducted in mice, demonstrated that Fli-1 directs key activation programs within HSPCs, allowing them to adapt to the vascular niche and respond to external signals. Notably, Fli-1 primes these cells to propagate angiocrine Notch1 signalling, a pathway that is vital for stem cell activation and functional recovery. Remarkably, the activation of Notch1 signalling alone was able to restore the function of HSPCs in the absence of Fli-1, without causing harmful leukemic transformations.
Furthermore, the researchers applied their findings to human cells, introducing FLI-1 modified-mRNA into latent adult human HSPCs. This technique enhanced the cells’ ability to expand and successfully engraft, offering promising implications for regenerative medicine.
This research offers valuable new strategies for boosting immune function and blood cell regeneration, with the potential to improve treatments for blood disorders and enhance stem cell-based therapies.
Helena Bradbury, EMJ
Reference
Itkin Tomer et al. Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing. Nature Immunology. 2025;26(3):378-90.
