Pooled shRNA-based Runx1 genetic interaction screen in primary mouse hematopoietic cells. (A) Schematic of the shRNA screen. Lineage-depleted hematopoietic cells were isolated from femurs and tibias of 3 conditional Runx1-knockout mice (Runx1Δ/Δ). Cells were retrovirally transduced with a genome-wide shRNA library. Transduced cells were plated into methylcellulose containing stem cell factor, IL-3, IL-6, and erythropoietin. Cells were replated weekly into fresh methylcellulose. After 8 weeks of serial replating, remaining shRNAs were recovered and sequenced. (B) Runx1Δ/Δ Lin− cells transduced with the library formed colonies in methylcellulose for more than 8 weeks. Nontransduced cells were plated in triplicate. Error bars indicate the SDs of plating capacities from 3 independent experiments.