Mgbemena et al report that hematopoietic stem cells have an absolute requirement for Brca1 to survive. They also show that humanization of the mouse Brca1 e with a knocked-in BRCA1 cDNA, but not a mutant BRCA1/5382insC cDNA, fully substitutes for the mouse Brca1 during both embryonic development and hematopoiesis. Overall design: Enlarged spleens from 2-3 mo. old Brca1∆/∆ mice and Brca1+/+ mice were taken for RNA extraction and processed for paired-end RNA seq.