Towards determining the differentiation program of antigen-presenting dendritic cells by transcriptional profiling.
Dendritic cells (DC) represent professional antigen-presenting cells that develop from hematopoietic progenitors through successive steps of differentiation. Employing DNA microarray technology, we analysed the specific changes in gene expression that occur when human progenitor cells differentiate into DC. CD34 progenitor cells were first amplified in vitro with stem cell factor (SCF), Flt3 ligand (FL), thrombopoietin and IL-6/soluble IL-6 receptor fusion protein, and cells were then induced to differentiate into DC with IL-4 and GM-CSF. DC maturation was induced by TNFalpha. Progenitor cells and DC were subjected to transcriptional profiling by DNA microarrays that represent 13000 human genes. Our analysis revealed specific changes in the expression of a large number of cell surface antigens including molecules involved in antigen uptake and processing, cell migration and antigen presentation. Genes encoding such molecules were upregulated during DC differentiation as were genes encoding cytokines, cytokine receptors, chemokines and chemokine receptors. Stem cell genes and genes related to the multilineage differentiation potential and proliferative state of progenitor cells were downregulated. Our analysis also provides information on the expression profiles of transcriptional regulators such as the NF-kappaB/rel and STAT transcription factors. Interestingly, NF-kappaB/rel factors were found to be expressed in both progenitor cells and DC at similar levels and were induced by TNFalpha. In contrast, expression of STAT factors increased during DC differentiation and their expression was virtually unaffected by TNFalpha.
Ju
Xin-Sheng
XS
Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, Germany.
Hacker
Christine
C
Madruga
Jaime
J
Kurz
Steffen M
SM
Knespel
Siegne
S
Blendinger
Gitta
G
Rose-John
Stefan
S
Martin
Zenke
Z
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019707:Receptors, Chemokine / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018952:Antigens, CD34; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor