Identification of a stroma-mediated Wnt/β-catenin signal promoting self-renewal of hematopoietic stem cells in the stem cell niche

Cited 59 time in scopus
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Title
Identification of a stroma-mediated Wnt/β-catenin signal promoting self-renewal of hematopoietic stem cells in the stem cell niche
Author(s)
J A Kim; Y J Kang; G Park; M Kim; Y O Park; H Kim; S H Leem; In-Sun Chu; J S Lee; E H Jho; I H Oh
Bibliographic Citation
Stem Cells, vol. 27, no. 6, pp. 1318-1329
Publication Year
2009
Abstract
With contrasting observations on the effects of β-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt/β-catenin signals on HSC regulation remains unclear. Here, we show a distinct mode of Wnt/β-catenin signal that can regulate HSCs in a stroma-dependent manner. Stabilization of β-catenin in the bone marrow stromal cells promoted maintenance and self-renewal of HSCs in a contact-dependent manner, whereas direct stabilization in hematopoietic cells caused loss of HSCs. Interestingly, canonical Wnt receptors and β-catenin accumulation were predominantly enriched in the stromal rather than the hematopoietic compartment of bone marrows. Moreover, the active form of β-catenin accumulated selectively in the trabecular endosteum in "Wnt 3a-stimulated" or "irradiationstressed," but not in "steady-state" marrows. Notably, notch ligands were induced in Wnt/β-catenin activated bone marrow stroma and downstream notch signal activation was seen in the HSCs in contact with the activated stroma. Taken together, Wnt/β-catenin activated stroma and their cross-talk with HSCs may function as a physiologically regulated microenvironmental cue for HSC self-renewal in the stem cell niche.
Keyword
Hematopoietic stem cellSelf-renewalStem cell-microenvironment interactionsStromaWNT
ISSN
1066-5099
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/stem.52
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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