Transcriptome Characterization Uncovers the Molecular Response of Hematopoietic Cells to Ionizing Radiation
| Autor: | Diana Tronik-Le Roux, Pierre Vaigot, Sylvain Baulande, Olivier Alibert, Alexandre Pawlik |
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| Přispěvatelé: | Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris], Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, PartnerChip, Génopole, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Therapie Genique Hematopoietique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by funds from the Commissariat à l'Energie Atomique (CEA) and Electricité de France (EDF), We would like to thank Dr. G. Gruel and Florian Alonso for their assistance in the initial development of the strategy, Marie-Eve Schodet and Hakim Ouled Haddou for assistance on the purification and analysis of LT-HSC, and the PartnerChip team, directed by Pascal Soularue, for excellent Affymetrix microarray support. We also thank Christophe Joubert and Claire Chauveau for their outstanding work in animal care., Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
MESH: Gene Expression Profiling Gene regulatory network MESH: Antigens CD / genetics Radiation Tolerance Transcriptome Mice 0302 clinical medicine MESH: Reverse Transcriptase Polymerase Chain Reaction Gene expression MESH: Animals Oligonucleotide Array Sequence Analysis 0303 health sciences Membrane Glycoproteins Radiation MESH: Radiation Tolerance Reverse Transcriptase Polymerase Chain Reaction Cell biology Haematopoiesis medicine.anatomical_structure MESH: Connexin 43 / physiology 030220 oncology & carcinogenesis MESH: Mice Transgenic Biophysics Immunoglobulins Mice Transgenic MESH: Tumor Suppressor Protein p53 / deficiency Biology MESH: Membrane Glycoproteins / genetics 03 medical and health sciences Antigens CD MESH: Mice Inbred C57BL [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] medicine Animals Radiology Nuclear Medicine and imaging Gene Transcription factor MESH: Mice 030304 developmental biology Binding Sites MESH: Hematopoietic Stem Cells / metabolism MESH: Immunoglobulins / genetics Gene Expression Profiling Hematopoietic Stem Cells Molecular biology MESH: Male Mice Inbred C57BL MESH: Binding Sites MESH: Hematopoietic Stem Cells / radiation effects Connexin 43 Molecular Response MESH: Oligonucleotide Array Sequence Analysis Bone marrow Tumor Suppressor Protein p53 |
| Zdroj: | Radiation Research Radiation Research, Radiation Research Society, 2011, 175 (1), pp.66-82. ⟨10.1667/rr2282.1⟩ Radiation Research, 2011, 175 (1), pp.66-82. ⟨10.1667/rr2282.1⟩ |
| ISSN: | 0033-7587 |
| DOI: | 10.1667/rr2282.1⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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