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

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/beta-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.

In this review, the biological outcomes of Wnt/beta-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/beta-catenin signals and studies that verify this concept is summarized.

We show that distinct effects of Wnt/beta-catenin on HSCs can be caused depending on their target of activation in the hematopoietic microenvironment. We show stromal targeting of Wnt/beta-catenin signals and cross-talk with notch signals in the niche during bone marrow regeneration enhancing the self-renewal of HSCs.

The identification of stroma-mediated Wnt/beta-catenin effects now allows the integration of discrepancies in previously reported findings and suggests that the stromal targeting of wnt/beta-catenin signals could serve as a potential therapeutic strategy for activating a stem cell niche for the efficient regeneration of HSCs.