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Innovative Research Unveils New Insights into Blood Cell Development

A groundbreaking study spearheaded by researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center has introduced an innovative technique to explore the role of transcription factors in the regulation of genetic programs that govern cell growth and maturation. This method, termed “Perturb-multiome,” utilizes CRISPR technology to disrupt the functions of specific transcription factors across numerous blood cells simultaneously.

Through this systematic approach, the research team conducted single-cell analyses to assess the repercussions of these genetic modifications. They focused on which genes experienced activation or suppression, as well as the accessibility of various genes as determined by epigenetic markers. By applying this technique to immature blood cells, the investigators successfully pinpointed critical transcription factors and their corresponding DNA regions that play a pivotal role in blood cell development.

Interestingly, the study revealed that many of the identified DNA regions crucial for blood cell production also contain mutations associated with various blood disorders. While these significant regions make up less than 0.3% of the entire genome, they have a disproportionately large impact on the genetic aspects of blood cell characteristics and specialization.

In previous research efforts, this team, along with collaborators, utilized genome-wide association studies to identify a transcription factor that plays a key role in switching off fetal hemoglobin after birth. This foundational work has paved the way for advancements in gene therapy aimed at treating conditions such as sickle cell disease and beta thalassemia.

The Perturb-multiome strategy offers researchers a powerful tool to comprehensively examine how thousands of variations in transcription factors affect blood cell production and associated disease risks. This advancement opens the door to a broader discovery of targeted therapies for blood disorders, potentially transforming treatment options for patients.

Funding: The research was supported by the La Caixa Foundation, the Rafael del Pino Foundation, the American Society of Hematology, the Broad Institute, the New York Stem Cell Foundation, the Lodish Family, the Howard Hughes Medical Institute, and the National Institutes of Health.

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