| Literature DB >> 19664990 |
Jonas Renström1, Rouzanna Istvanffy, Kerstin Gauthier, Akihiko Shimono, Jörg Mages, Ana Jardon-Alvarez, Monika Kröger, Matthias Schiemann, Dirk H Busch, Irene Esposito, Roland Lang, Christian Peschel, Robert A J Oostendorp.
Abstract
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.Entities:
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Year: 2009 PMID： 19664990 DOI： 10.1016/j.stem.2009.05.020
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633