Single-cell CRISPR screen maps epigenetic regulators of lineage specification and malignancies in human HSPCs.

Single-cell CRISPR screening in human HSPCs identified regulators like SMYD3 and PRDM10 linked to cell fate and AML dependency, with 322 regulators profiled in 172,382 cells.

• Why it matters: Understanding how genetic perturbations influence cell fate is crucial for insights into human development and disease, especially in hematopoietic stem cells and leukemia.
• What they did: A scalable single-cell CRISPR platform was developed to profile 322 regulators across over 172,000 primary human HSPCs, revealing regulator-phenotype relationships and gene programs.
• The result: The atlas identified regulators such as SMYD3 as a negative regulator of regenerative capacity and PRDM10 as a candidate dependency in AML, enabling functional annotation of lineage and disease mechanisms.