A groundbreaking study spearheaded by researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center has introduced an innovative method to decipher the mechanisms behind cell growth and maturation. By employing a novel technique named “Perturb-multiome,” scientists are able to simultaneously disable specific transcription factors in numerous blood cells using CRISPR technology. Following this intervention, each cell undergoes single-cell analysis to evaluate the impact on gene expression and accessibility. This approach not only identifies genes activated or deactivated but also uncovers which genetic regions play crucial roles in shaping blood cell development.

The application of Perturb-multiome to immature blood cells has revealed key transcription factors and their corresponding DNA sequences that significantly influence blood cell evolution. Interestingly, many of these critical DNA regions are linked to mutations associated with various blood disorders. Despite occupying less than 0.3% of the genome, these regions exert a substantial influence on blood cell characteristics and specialization. The discovery provides profound insights into how specific genetic elements control blood cell production and contribute to disease susceptibility.

This research builds upon previous findings where the team identified the transcription factor responsible for turning off fetal hemoglobin post-birth, paving the way for potential gene therapies for sickle cell disease and beta-thalassemia. The Perturb-multiome technique now allows for a systematic exploration of thousands of transcription factor variations, enhancing our understanding of their roles in blood cell generation and disease risk. Such advancements open doors to discovering additional targeted therapies for blood-related ailments, fostering hope for improved patient outcomes and healthier futures worldwide.