Transcriptional regulation of self-renewal in human haematopoietic stem cells

Bone marrow transplants often fail because scientists cannot yet grow enough blood stem cells in the lab to treat patients reliably. The problem is that no one fully understands how these cells—called haematopoietic stem cells (HSCs)—decide to copy themselves instead of turning into specialised blood cells. This project aims to crack that decision-making process by tracking how the cell’s metabolism and its gene-reading machinery interact. Specifically, the researcher will investigate how nutrients available to the cell influence whether RNA polymerase II pauses or pushes forward along DNA, and how chemical tags on chromatin alter the rate of gene transcription. By manipulating these levers, the team hopes to keep HSCs self-renewing in culture indefinitely. If successful, this work would make it possible to generate large numbers of transplantable HSCs from a patient’s own induced pluripotent stem cells, eliminating the need for donor matches and the risk of graft-versus-host disease. The findings could also illuminate why some cancer stem cells resist chemotherapy by entering a dormant, self-renewing state. This is fundamentally curiosity-driven research into the molecular logic of stemness, but past discoveries about transcriptional pausing and metabolism have already reshaped cancer drug development and regenerative medicine.