New study develops genetic screening methods for hematopoietic cells

Researchers introduced methods for analyzing genetic variants in human blood and immune cells, leading to insights in leukemia immunotherapy and the understanding of diverse diseases related to hematopoiesis. The study by Jorge Martin-Rufino, Nicole Castano, Vijay Sankaran, and others was published on May 25, 2023. 

According to the study, researchers focused on the assessment of genetic variants and their impact on human health and disease treatment. This study introduces a comprehensive approach to genome engineering, specifically addressing the challenge of applying these techniques to primary cells like blood and immune cells. By developing a new method of “massively parallel base-editing screens in human hematopoietic stem and progenitor cells,” the research allows for a detailed examination of variant effects across various stages of hematopoietic differentiation.

This technique not only facilitates functional screenings in primary human hematopoietic stem and progenitor cells but also incorporates single-cell RNA sequencing (scRNA-seq) for in-depth analysis, per the study. The use of scRNA-seq, akin to strategies employed in other genome-editing research, plays a role in understanding complex biological processes, states the study. Additionally, the study highlights the effectiveness of pooled single-cell genotyping, a method separate from base-editing screens, to swiftly and accurately evaluate the outcomes of genetic editing, aiding in the interpretation of the screening results.

The study's methodologies reportedly have implications for advancing the understanding and treatment of various diseases. By employing these base-editing screens and genotyping techniques, the research claims to design new approaches to leukemia immunotherapy, identify non-coding variants that influence fetal hemoglobin expression, elucidate mechanisms governing hematopoietic differentiation, and investigate uncharacterized disease-associated variants. The study states that these advancements in genetic screening and analysis could enhance the mapping of variant functions in human hematopoiesis, contributing to the identification of the causes behind a range of diseases.

Elsevier: Vijay Sankaran, Jorge D. Martin-Rufino, et al., Massively parallel base editing to map variant effects in human hematopoiesis, Cell (2023). https://doi.org/10.1016/j.cell.2023.03.035