Wnt signaling in the stem cell niche : Current Opinion in Hematology (original) (raw)
Hematopoiesis
aDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina; bSanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands
Supported by the Cancer Research Institute Investigator award, Ellison Medical Foundation New Scholar Award, and funds from the National Institutes of Health (T.R.).
Correspondence to Tannishtha Reya, Department of Pharmacology and Cancer Biology, LSRC C333 Duke University Medical Center, Durham, NC 27710 USA
Tel: 919 613 8756; fax: 919 668 3556; e-mail: [email protected]
Abstract
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 reports 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 in HSC biology.
© 2004 Lippincott Williams & Wilkins, Inc.