Identification of in vitro HSC fate regulators by differential lipid raft clustering.

Details

Serval ID
serval:BIB_F9B88A4797BA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of in vitro HSC fate regulators by differential lipid raft clustering.
Journal
Cell Cycle
Author(s)
Vannini N., Roch A., Naveiras O., Griffa A., Kobel S., Lutolf M.P.
ISSN
1551-4005 (Electronic)
ISSN-L
1551-4005
Publication state
Published
Issued date
2012
Volume
11
Number
8
Pages
1535-1543
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Most hematopoietic stem cells (HSC) in the bone marrow reside in a quiescent state and occasionally enter the cell cycle upon cytokine-induced activation. Although the mechanisms regulating HSC quiescence and activation remain poorly defined, recent studies have revealed a role of lipid raft clustering (LRC) in HSC activation. Here, we tested the hypothesis that changes in lipid raft distribution could serve as an indicator of the quiescent and activated state of HSCs in response to putative niche signals. A semi-automated image analysis tool was developed to map the presence or absence of lipid raft clusters in live HSCs cultured for just one hour in serum-free medium supplemented with stem cell factor (SCF). By screening the ability of 19 protein candidates to alter lipid raft dynamics, we identified six factors that induced either a marked decrease (Wnt5a, Wnt3a and Osteopontin) or increase (IL3, IL6 and VEGF) in LRC. Cell cycle kinetics of single HSCs exposed to these factors revealed a correlation of LRC dynamics and proliferation kinetics: factors that decreased LRC slowed down cell cycle kinetics, while factors that increased LRC led to faster and more synchronous cycling. The possibility of identifying, by LRC analysis at very early time points, whether a stem cell is activated and possibly committed upon exposure to a signaling cue of interest could open up new avenues for large-scale screening efforts.
Keywords
Animals, Cell Division, Cell Proliferation, Cluster Analysis, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/metabolism, Interleukin-3/metabolism, Interleukin-6/metabolism, Membrane Microdomains/metabolism, Mice, Mice, Inbred C57BL, Osteopontin/metabolism, Vascular Endothelial Growth Factor A/metabolism, Wnt Proteins/metabolism, Wnt3A Protein/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/05/2012 19:47
Last modification date
20/08/2019 17:25
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