Osteoblastic overexpression of Wif1 alters HSC potential in a context-dependent manner. (A) In Wif1 Tg mice in homeostatic conditions, osteoblasts have increased expression of HSC regulatory molecules such as Jag 1, Cdh2, Cxcl12, Bmp4, and Shh. HSCs have elevated expression of Wnt3a, Gli1, and Ptch1. Increased numbers of cycling HSCs are observed but the HSCs have normal serial transplantation potential. (B) In stress situations (such as 5-FU), osteoblastic expression of HSC-regulatory molecules is reduced in Wif1 Tg mice compared with that expressed in homeostasis (with the exception of Cxcl12, which is maintained). Wif1 Tg HSCs maintain high expression of Wnt3a, but down-regulate Gli1 and Ptch1 and up-regulate expression of Notch1, Hes1, and Cxcr4. The cell-cycle status of the HSCs was not determined, but HSCs lose their serial transplantation ability.