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Microenvironmental targeting of Wnt/β-catenin signals for hematopoietic stem cell regulation

Importance of the field: Microenvironment has emerged as crucial element in the regulation of hematopoietic stem cells (HSCs) in the stem cell niche. Recent studies have demonstrated that Wnt/β-catenin signals are clearly involved in the stem cell niche, raising the possibility that the hematopoietic microenvironment is a potential target for stem cell therapy. Areas covered in this review: In this review, the biological outcomes of Wnt/β-catenin signals on HSC activity are summarized in various study models and potential reasons for discrepancies are discussed. Evidence for the microenvironmental targeting of Wnt/β-catenin signals and studies that verify this concept is summarized. What the reader will gain: We show that distinct effects of Wnt/β-catenin on HSCs can be caused depending on their target of activation in the hematopoietic microenvironment. We show stromal targeting of Wnt/β-catenin signals and cross-talk with notch signals in the niche during bone marrow regeneration enhancing the self-renewal of HSCs. Take home message: The identification of stroma-mediated Wnt/β-catenin effects now allows the integration of discrepancies in previously reported findings and suggests that the stromal targeting of wnt/β-catenin signals could serve as a potential therapeutic strategy for activating a stem cell niche for the efficient regeneration of HSCs.