Stem cell homeostasis by integral feedback through the niche.

•Stem cell homeostasis is proposed to be based on bidirectional signaling between stem and niche cells.•The niche mediates integral negative feedback.•The model explains apparently contradictory experimental data on the recovery of hematopoietic stem cells after perturbation.•Niche cells may far outnumber stem cells.•Stem cell affinity for the niche may regulate output of differentiated cells.