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Renström, J.* ; Istvanffy, R.* ; Gauthier, K.* ; Shimono, A.* ; Mages, J.* ; Jardon-Alvarez, A.* ; Kröger, M.* ; Schiemann, M. ; Busch, D.H. ; Esposito, I. ; Lang, R.* ; Peschel, C.* ; Oostendorp, R.A.*

Secreted frizzled-related protein 1 extrinsically regulates cycling activity and maintenance of hematopoietic stem cells.

Cell Stem Cell 5, 157-167 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Secreted frizzled-related protein 1 (Sfrp1) is highly expressed by stromal cells maintaining hematopoietic stem cells (HSCs). Sfrp1 loss in stromal cells increases production of hematopoietic progenitors, and in knockout mice, dysregulates hemostasis and increases Flk2- Cd34- Lin- Sca1+ Kit+ (LSK) cell numbers in bone marrow. Also, LSK and multipotent progenitors (MPPs) resided mainly in the G0/G1 phase of cell cycle, with an accompanying decrease in intracellular beta-catenin levels. Gene-expression studies showed a concomitant decrease Ccnd1 and Dkk1 in Cd34- LSK cells and increased expression of Pparg, Hes1, and Runx1 in MPP. Transplantation experiments showed no intrinsic effect of Sfrp1 loss on the number of HSCs or their ability to engraft irradiated recipients. In contrast, serial transplantations of wild-type HSCs into Sfrp1(-/-) mice show a progressive decrease of wild-type LSK and MPP numbers. Our results demonstrate that Sfrp1 is required to maintain HSC homeostasis through extrinsic regulation of beta-catenin.
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Publication type Article: Journal article
Document type Scientific Article
Keywords canonical WNT pathway; beta-catenin; self-renewal; long-term; stromal cells; tumor-suppressor; down-regulation; gamma-catenin; DNA-binding; in-vivo
Language english
Publication Year 2009
HGF-reported in Year 2009
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Journal Cell Stem Cell
Quellenangaben Volume: 5, Issue: 2, Pages: 157-167 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
CCG Immune Monitoring (Platform) (IMI-KIM)
Institute of Pathology (PATH)
Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection

Enabling and Novel Technologies
PSP Element(s) G-520100-001
G-520400-001
G-500300-001
G-501700-005
PubMed ID 19664990
DOI 10.1016/j.stem.2009.05.020
Scopus ID 67849122659
Erfassungsdatum 2009-12-07
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