Retroviral integration sites correlate with expressed genes in hematopoietic stem cells.
In this study, we analyzed whether retroviral integration sites in repopulating hematopoietic cells correlate with genes expressed in fractions enriched in hematopoietic stem cells (HSCs). We have previously described microarray studies of two populations enriched in HSCs: CD34+/CD38- and the slow dividing fraction of CD34+/CD38- cells (SDF). Furthermore, we demonstrated that oncoretroviral integrations in severe combined immunodeficient repopulating cells are preferentially located near the transcription start. Here, we have identified 117 corresponding cDNA clones on our micro-array representing genes with retroviral integration sites. These genes revealed a higher mean signal intensity in comparison with either all genes on the array or a subset of control genes with retroviral integrations in HeLa cells. Furthermore, these genes demonstrated a higher expression in CD34+/CD38- cells and SDF. The association of gene expression and retrovirally targeted genes observed here will help to elucidate the molecular characteristics of primitive repopulating hematopoietic cells.
Wagner
Wolfgang
W
Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Laufs
Stephanie
S
Blake
Jonathon
J
Schwager
Christian
C
Wu
Xiaolin
X
Zeller
Jens W
JW
Ho
Anthony D
AD
Fruehauf
Stefan
S
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D006367:HeLa Cells; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D012190:Retroviridae / Q000235:genetics*; D024363:Transcription Initiation Site; D014161:Transduction, Genetic; D016662:Virus Integration / Q000235:genetics*
D018952:Antigens, CD34