Prdm16 is one of a handful of genes that are known to be required for the maintenance and integrity of hematopoietic stem cells. Other genes include Bmi1, Evi1, Pbx1, Gfi1, and the FoxO transcription factors. The balanced activity of these nuclear factors preserves the stem cell state but is constantly challenged by external cues and stress from the environment. Professional illustration by Alice Chen.