PURPOSE OF REVIEW: All the cells present in the blood are derived from the hematopoietic stem cell (HSC). Because mature blood cells have a limited life span, HSCs must perpetuate themselves through self-renewal to maintain a functional hematopoietic compartment for the lifetime of an organism. This review focuses on studies that identify the Wnt signaling pathway as a mediator of HSC self-renewal and maintenance and analyzes its potential influence in context of the HSC niche. RECENT FINDINGS: The Wnt signaling pathway has emerged as a potential regulator of self-renewal for HSCs. Recent findings have demonstrated that Wnt signaling can directly promote HSC self-renewal and ability to reconstitute the hematopoietic system of lethally irradiated mice. The recent findings that osteoblasts are an important regulatory component of the HSC microenvironment, and that elements of the Wnt signaling pathway can influence osteoblast frequency, raise the possibility that Wnt signaling may influence HSC function indirectly through the niche as well. SUMMARY: 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.
PURPOSE OF REVIEW: All the cells present in the blood are derived from the hematopoietic stem cell (HSC). Because mature blood cells have a limited life span, HSCs must perpetuate themselves through self-renewal to maintain a functional hematopoietic compartment for the lifetime of an organism. This review focuses on studies that identify the Wnt signaling pathway as a mediator of HSC self-renewal and maintenance and analyzes its potential influence in context of the HSC niche. RECENT FINDINGS: The Wnt signaling pathway has emerged as a potential regulator of self-renewal for HSCs. Recent findings have demonstrated that Wnt signaling can directly promote HSC self-renewal and ability to reconstitute the hematopoietic system of lethally irradiated mice. The recent findings that osteoblasts are an important regulatory component of the HSC microenvironment, and that elements of the Wnt signaling pathway can influence osteoblast frequency, raise the possibility that Wnt signaling may influence HSC function indirectly through the niche as well. SUMMARY: 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.
Authors: Sachin Malhotra; Yoshihiro Baba; Karla P Garrett; Frank J T Staal; Rachel Gerstein; Paul W Kincade Journal: J Immunol Date: 2008-09-15 Impact factor: 5.422