It is well established that Wnt can directly influence HSCs; however Wnt also regulates MSCs, which become more supportive of hematopoiesis. Ichii and coworkers show that this is at least in part mediated by Wnt-dependent production of extracellular matrix component Decorin, thereby proving a Wnt-dependent cross-talk between MSCs and HSCs. Professional illustration by A. Y. Chen.