Generation of hemogenic endothelium enables HSC-like self-renewal and lineage potential. By first making hemogenic endothelium, either by directed differentiation of PSCs or reprogramming endothelial cells from various tissues and expressing pools of transcription factors, full lineage potential and HSC self-renewal could be achieved. (SB431542 is an inhibitor of Activin/Nodal signaling, and CHIR99021 is a GSK-3 inhibitor.)