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Original Article |
1 Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
2 Biochemical Instrumentation Program, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany
* To whom correspondence should be addressed. E-mail: anthony_dick.ho{at}urz.uni-heidelberg.de.
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Abstract |
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Cell-cell contact between stem cells and cellular determinants of the microenvironment plays an essential role in controlling cell division. Using human hematopoietic progenitor cells (CD34+/CD38-) and a stroma cell line (AFT024) as a model, we have studied the initial behavioral and molecular sequel of this interaction. Time-lapse microscopy showed that CD34+/CD38- cells actively migrated towards and sought contact with stroma cells and 30% of them adhered firmly to AFT024 stroma through the uropod. CD44 and CD34 are co-localized at the site of contact. Gene expression profiles of CD34+/CD38- cells upon cultivation with or without stroma for 16h, 20h, 48h or 72h were analyzed using our Human Genome cDNA Microarray. Chk1, egr1 and cxcl2 were among the first genes up-regulated within 16h. Genes with the highest up-regulation throughout the time course included tubulin genes, ezrin, c1qr1, fos, pcna, mcm6, ung and dnmt1, genes that play an essential role in re-organization of the cytoskeleton system, stabilization of DNA and of methylation patterns. Our results demonstrate directed migration of CD34+/CD38- cells towards AFT024, adhesion through the uropod and that upon interaction with supportive stroma, re-organization of the cytoskeleton system, regulation of cell division and maintenance of genetic stability represent the most essential steps.
Key Words. Hematopoietic stem cell, Microenvironment, Uropod, Adhesion, Microarray
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