title: Transcriptome characterization uncovers the molecular response of hematopoietic cells to ionizing radiation.
abstract: Ionizing radiation causes rapid and acute suppression of hematopoietic cells that manifests as the hematopoietic syndrome. However, the roles of molecules and regulatory pathways induced in vivo by irradiation of different hematopoietic cells have not been completely elaborated. Using a strategy that combined different microarray bioinformatics tools, we identified gene networks that might be involved in the early response of hematopoietic cells radiation response in vivo. The grouping of similar time-ordered gene expression profiles using quality threshold clustering enabled the successful identification of common binding sites for 56 transcription factors that may be involved in the regulation of the early radiation response. We also identified novel genes that are responsive to the transformation-related protein 53; all of these genes were biologically validated in p53-transgenic null mice. Extension of the analysis to purified bone marrow cells including highly purified long-term hematopoietic stem cells, combined with functional classification, provided evidence of gene expression modifications that were largely unknown in this primitive population. Our methodology proved particularly useful for analyzing the transcriptional regulation of the complex ionizing radiation response of hematopoietic cells. Our data may help to elucidate the molecular mechanisms involved in tissue radiosensitivity and to identify potential targets for improving treatment in radiation emergencies.
authors.affiliation: Institut Pasteur, Paris.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pawlik
authors.forename: Olivier
authors.initials: O
authors.lastname: Alibert
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baulande
authors.forename: Pierre
authors.initials: P
authors.lastname: Vaigot
authors.forename: Diana
authors.initials: D
authors.lastname: Tronik-Le Roux
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001665:Binding Sites; D018031:Connexin 43 / Q000502:physiology; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D007136:Immunoglobulins / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018031:Connexin 43; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D016159:Tumor Suppressor Protein p53; D000097802:CD83 Antigen