Scientists at Dana-Farber Cancer Institute have developed ‘Perturb-multiome,’ a groundbreaking genomic screening method that enables precise reverse-engineering of genetic programming in cells, offering new avenues for understanding and treating blood disorders.
Key Points at a Glance
- Perturb-multiome combines CRISPR gene editing with single-cell analyses to investigate transcription factors in blood cell development.
- The method identifies crucial DNA regions influencing blood cell maturation, many linked to blood disorders.
- Findings could lead to novel targeted therapies for various blood-related diseases.
Deciphering the complex genetic instructions that govern cellular development has long been a challenge in biomedical research. Transcription factors—proteins that regulate gene expression—play a pivotal role in determining cell fate. Understanding their influence is crucial, especially in the context of blood cell formation and associated disorders.
Researchers at Dana-Farber Cancer Institute have introduced ‘Perturb-multiome,’ an innovative approach that merges CRISPR gene-editing technology with single-cell RNA sequencing. This method allows for the simultaneous inactivation of multiple transcription factors across numerous blood cells, followed by detailed analyses of gene expression and chromatin accessibility in each cell.
Applying Perturb-multiome to immature blood cells, the team identified specific transcription factors and corresponding DNA regions that significantly impact blood cell development. Notably, many of these regions coincide with genetic mutations previously linked to various blood disorders. Although these critical DNA segments comprise less than 0.3% of the entire genome, they account for a disproportionately large influence on blood cell characteristics and specialization.
This advancement builds upon earlier research where genome-wide association studies pinpointed transcription factors responsible for deactivating fetal hemoglobin post-birth. Such foundational work has been instrumental in developing gene therapies for conditions like sickle cell disease and beta-thalassemia. Perturb-multiome’s comprehensive approach now offers a systematic means to explore how numerous transcription factor variants affect blood cell production and disease susceptibility, potentially paving the way for a broader spectrum of targeted treatments for blood disorders.
The study, titled “Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes,” was published in the journal Science.
