Wnt signaling in the stem cell niche

Abstract

In this review, the authors evaluate the experimental evidence for a direct role of Wnt signaling HSCs as well as an indirect role through its influence on the HSC niche. Defining the mechanism of action of Wnt signaling in HSC maintenance in context of the surrounding microenvironment and determining how this signal may integrate with other niche derived signals represents the next challenge HSC biology.

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells

“…The hematopoietic microenvironment contains the putative stem cell 'niche' and is composed of hematopoietic and non-hematopoietic (cellular and extracellular) components, 40,41 thought to provide the complex molecular cues that direct HPC self-renewal and proliferation and regulate the differentiation and maturation of hematopoietic progeny. [42][43][44][45][46][47] This would be consistent with the observation that ex vivo contact with stromal components of the hematopoietic microenvironment preserves hematopoietic stem cell activity. [48][49][50][51][52][53] One component of the hematopoietic microenvironment, mesenchymal stem cells (MSCs), can be isolated as plastic adherent cells from a variety of fetal and adult tissues.…”

Stem Cell Niche, the Microenvironment and Immunological Crosstalk

“…The formulation of stromal structure engraved in the form of a matrix and their role in constituting microenvironmental nest the niche has been indicated in our previous citation (24). The details of the mystery of crosstalk between the stromal cells for the generation of healthy stem cells are yet to explore but evidences are available that the cytokine mediated signaling represent the crosstalk in between stem and stroma for the subsequent development in the niche (25)(26)(27)(28). Other evidences are also outcoming to support the view that the "niche-stroma-stem apparatus" has spontaneous crosstalk via cytokine mediated regulatory molecules for specifically directed differentiation and growth ( Figure 1).…”

The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia

“…83 Several studies revealed a critical role of Wnt signaling for communication between HSCs and cells of the microenvironment, and particularly with osteoblasts. [78][79][80]84,85 These interactions also contribute to HSC self-renewal.…”

“…74 Apparently, HSCs are able to synthesize Wnt proteins binding to the Frizzled-LRP5/6-receptor complex, suggesting an autocrine or paracrine mechanism for the stimulation of selfrenewal through Wnt signaling in those cells. [78][79][80] Furthermore, recent findings indicate that Wnt proteins are not only produced by HSCs themselves but are also released from bone marrow stromal cells. 23,77,81,82 Within the bone marrow, HSCs reside in small niches and are surrounded by other cells and matrix components constituting the microenvironment.…”