Hematopoietic stem cells are coordinated by the molecular cues of the endosteal niche

Hematopoietic stem cells (HSCs) accomplish a complex task. On a daily base billions of the 8 different mature cells are delivered in the right proportions. HSCs are located in niches located at several locations in the body. Communication between these spatially separated niches is accomplished by stem cells that leave their niche and migrate to other niches guided by soluble factors. The niche itself comprises all major signaling pathways (Hedgehog, Notch, Wnt, and BMP) and an array of adhesion molecules. The interplay between these components keep HSC in a quiescent state but also speed up production in case of urgent need during infection or excessive blood loss. In this review, we focus on the molecular cues of the niche, functional adhesion molecules and describe recent data obtained with multiphoton microscopy. A vast array of molecules is described that display similar functions as HSC controllers. This points to redundancy in the system that enables HSC to respond to different cues essentially with the same functional response. Apparently, the hematopoietic system is so crucial that it is not dependent on a single cue. When one cue fails to initiate a response, another cue will take over leading to an almost similar response. Another explanation is that every cue adds to an integrated signal that results in reaching the threshold. This integrated signal might be reached from huge signaling by a single cue or the low but additive signals by several cues.