We have previously reported that marrow stem cells show changes in engraftment (

Habibian, et al
J Ex. Hem
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188
:
393
–398,
1998
), homing (
Cerny et al.,
J Hematother Stem Cell Res
11
:
913
–922,
2002
) and differentiation (
Colvin et al.,
J Cell Phys
199
:
20
–31,
2004
) phenotype as they transit a cytokine-driven cell cycle. mRNA and surface expression of adhesion proteins also change (
Becker et al.,
Exp Hematol
27
:
533
–541,
1999
). We have evaluated gene expression by Real-time PCR of murine lineage negative, Sca+ (Lin-Sca+) stem cells stimulated by Il-3, Il-6, Il-11 and Steel factor (at 0, 24 and 48h) and lineage negative Rhodamine low, Hoescht low (LRH) stem cells stimulated by TPO, Flt-3 and Steel at various points in cell cycle transit (0,32,40,48h). In Lin-Sca+ cells (4experiments, time 0) expression of the following genes in descending order was as follows: IKAROS, L-selectin, Pu-1, Gata-2, Pecam, Cd84, Rock-1, c-fms, FOG, Cxcr4, c-kit, Cd4. The following were either not expressed or expressed at very low levels: Il-11, Ccr4, Sdf-1, Gata-1, P-selectin and Vecam. A pattern of depressed gene expression in S-phase (24h) with subsequent recovery (48h) was seen with c-fms and c-kit. With LRH cells (2 experiments, time 0) approximate descending rank order of gene expression was Cd45r, Cd34, G-CSFR, Mac-1, GM-CSFR and Flt-3. Il7r was not detected. With cycle progression Cd34 and Sca-1 were markedly elevated while Mac-1 and c-mpl were decreased. The expression of GM-CSFR, G-CSFR, Cd45r and Cd4 showed variable fluctuation. Il-7r was negative throughout. These data show that primitive marrow stem cells express a wide variety of “hematopoietic genes”, that expression modulates with cell cycle transit and perhaps most importantly that observed changes in gene expression are reversible. This is consistent with the continuum theory of stem cell regulation.

Topics:
adhesions, cd34 antigens, cell cycle, cxcr4 receptors, cytokine, gata1 protein, human, gene expression, interleukin 7 receptor, interleukin-11, interleukin-3

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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