Document Detail


The canonical Wnt pathway shapes niches supportive of hematopoietic stem/progenitor cells.
MedLine Citation:
PMID:  22117039     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Considerable information has accumulated about components of BM that regulate the survival, self-renewal, and differentiation of hematopoietic cells. In the present study, we investigated Wnt signaling and assessed its influence on human and murine hematopoiesis. Hematopoietic stem/progenitor cells (HSPCs) were placed on Wnt3a-transduced OP9 stromal cells. The proliferation and production of B cells, natural killer cells, and plasmacytoid dendritic cells were blocked. In addition, some HSPC characteristics were maintained or re-acquired along with different lineage generation potentials. These responses did not result from direct effects of Wnt3a on HSPCs, but also required alterations in the OP9 cells. Microarray, PCR, and flow cytometric experiments revealed that OP9 cells acquired osteoblastic characteristics while down-regulating some features associated with mesenchymal stem cells, including the expression of angiopoietin 1, the c-Kit ligand, and VCAM-1. In contrast, the production of decorin, tenascins, and fibromodulin markedly increased. We found that at least 1 of these extracellular matrix components, decorin, is a regulator of hematopoiesis: upon addition of this proteoglycan to OP9 cocultures, decorin caused changes similar to those caused by Wnt3a. Furthermore, hematopoietic stem cell numbers in the BM and spleen were elevated in decorin-knockout mice. These findings define one mechanism through which canonical Wnt signaling could shape niches supportive of hematopoiesis.
Authors:
Michiko Ichii; Mark Barton Frank; Renato V Iozzo; Paul W Kincade
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-23
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-05-01     Revised Date:  2013-04-12    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1683-92     Citation Subset:  AIM; IM    
Affiliation:
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Cell Differentiation / genetics
Cell Proliferation
Cells, Cultured
Gene Expression Profiling
Hematopoiesis / genetics
Hematopoietic Stem Cells / cytology*,  metabolism,  physiology*
Humans
Infant, Newborn
Lymphopoiesis / genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Microarray Analysis
Stem Cell Niche / genetics,  physiology*
Wnt Signaling Pathway / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
AI020069/AI/NIAID NIH HHS; CA39481/CA/NCI NIH HHS; R01 CA039481/CA/NCI NIH HHS
Comments/Corrections
Comment In:
Blood. 2012 Feb 16;119(7):1618-9   [PMID:  22343661 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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