Model of secreted and cell-associated factors produced by osteoblasts that influence HSCs. Stem cell fate is influenced by specialized microenvironments that remain poorly defined. Osteoblast production of soluble hematopoietic supportive–secreted and cell-associated factors work in concert so that hematopoietic stem cells derive regulatory information from bone, accounting for the localization of hematopoiesis in bone marrow. Alk P04 indicates alkaline phosphatase; BG, byglycan; BMPs, bone morphogenic factors; ColI, collagen type I; FGFs, fibroblast growth factors; FL, Flt ligand; FM, fibromodulin; FN, fibronectin; HGF, hepatocyte growth factor; HS, heparin sulfate proteoglycan; IGFs, insulinlike growth factors; IFN, interferon; JE/MCP-1, JE/monocyte chemotactic protein-1; MGP, matrix Gla protein; OC, osteocalcin; ON, osteonectin; ONC-M, oncostatin-M; OP, osteopontin; PDGF, platelet-derived growth factor; PF4, platelet factor 4; RSTK, serine/threonine kinase receptor; RTK, tyrosine kinase receptor; and TP, thrombospondin.