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  • Title: Identification of a stroma-mediated Wnt/beta-catenin signal promoting self-renewal of hematopoietic stem cells in the stem cell niche.
    Author: Kim JA, Kang YJ, Park G, Kim M, Park YO, Kim H, Leem SH, Chu IS, Lee JS, Jho EH, Oh IH.
    Journal: Stem Cells; 2009 Jun; 27(6):1318-29. PubMed ID: 19489023.
    Abstract:
    With contrasting observations on the effects of beta-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt/beta-catenin signals on HSC regulation remains unclear. Here, we show a distinct mode of Wnt/beta-catenin signal that can regulate HSCs in a stroma-dependent manner. Stabilization of beta-catenin in the bone marrow stromal cells promoted maintenance and self-renewal of HSCs in a contact-dependent manner, whereas direct stabilization in hematopoietic cells caused loss of HSCs. Interestingly, canonical Wnt receptors and beta-catenin accumulation were predominantly enriched in the stromal rather than the hematopoietic compartment of bone marrows. Moreover, the active form of beta-catenin accumulated selectively in the trabecular endosteum in "Wnt 3a-stimulated" or "irradiation-stressed," but not in "steady-state" marrows. Notably, notch ligands were induced in Wnt/beta-catenin activated bone marrow stroma and downstream notch signal activation was seen in the HSCs in contact with the activated stroma. Taken together, Wnt/beta-catenin activated stroma and their cross-talk with HSCs may function as a physiologically regulated microenvironmental cue for HSC self-renewal in the stem cell niche.
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