Expression of a retinoic acid signature in circulating CD34 cells from coronary artery disease patients.
BACKGROUND
Circulating CD34+ progenitor cells have the potential to differentiate into a variety of cells, including endothelial cells. Knowledge is still scarce about the transcriptional programs used by CD34+ cells from peripheral blood, and how these are affected in coronary artery disease (CAD) patients.


RESULTS
We performed a whole genome transcriptome analysis of CD34+ cells, CD4+ T cells, CD14+ monocytes, and macrophages from 12 patients with CAD and 11 matched controls. CD34+ cells, compared to other mononuclear cells from the same individuals, showed high levels of KRAB box transcription factors, known to be involved in gene silencing. This correlated with high expression levels in CD34+ cells for the progenitor markers HOXA5 and HOXA9, which are known to control expression of KRAB factor genes. The comparison of expression profiles of CD34+ cells from CAD patients and controls revealed a less naïve phenotype in patients' CD34+ cells, with increased expression of genes from the Mitogen Activated Kinase network and a lowered expression of a panel of histone genes, reaching levels comparable to that in more differentiated circulating cells. Furthermore, we observed a reduced expression of several genes involved in CXCR4-signaling and migration to SDF1/CXCL12.


CONCLUSIONS
The altered gene expression profile of CD34+ cells in CAD patients was related to activation/differentiation by a retinoic acid-induced differentiation program. These results suggest that circulating CD34+ cells in CAD patients are programmed by retinoic acid, leading to a reduced capacity to migrate to ischemic tissues.
van der Pouw Kraan
Tineke C T M
TC
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechorststraat, 1081BT Amsterdam, The Netherlands. t.vanderpouwkraan@vumc.nl
Schirmer
Stephan H
SH
Fledderus
Joost O
JO
Moerland
Perry D
PD
Baggen
Josefien M
JM
Leyen
Thomas A
TA
van der Laan
Anja M
AM
Piek
Jan J
JJ
van Royen
Niels
N
Horrevoets
Anton J G
AJ
D018952:Antigens, CD34 / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*
D018952:Antigens, CD34; D014212:Tretinoin