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Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells |
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| Authors: | Hideaki Nakajima Miyuki Ito Tadasuke Komori Fumi Shibata Toshio Kitamura |
| Institution: | a Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan b Center of Excellence, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan c Department of Anatomy and Neurobiology, Wakayama Medical College, Wakayama 641-8509, Japan d Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan |
| Abstract: | Wnt signaling has been implicated in the self-renewal of hematopoietic stem cells (HSCs). Secreted frizzled-related proteins (SFRPs) are a family of soluble proteins containing a region homologous to a receptor for Wnt, Frizzled, and are thought to act as endogenous modulators for Wnt signaling. This study examined the role of SFRPs in HSC regulation. Among the four family members, SFRP-1 and SFRP-2 are specifically induced in the bone marrow in response to myelosuppression, and immunostaining revealed that both proteins were expressed in osteoblasts. Interestingly, SFRP-1 reduced the number of multipotent progenitors in in vitro culture of CD34−KSL cells, while SFRP-2 did not. Furthermore, SFRP-1 compromised the long-term repopulating activity of HSCs, whereas SFRP-2 did not affect or even enhanced it in the same setting. These results indicate that although both SFRP-1 and SFRP-2 act as inhibitors for Wnt signaling in vitro, they differentially affect the homeostasis of HSCs. |
| Keywords: | Hematopoietic stem cells Secreted frizzled-related protein SFRP Wnt Self-renewal Osteoblast |
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