title: Identification of hub genes related to the recovery phase of irradiation injury by microarray and integrated gene network analysis.
abstract: BACKGROUND
  Irradiation commonly causes long-term bone marrow injury charactertized by defective HSC self-renewal and a decrease in HSC reserve. However, the effect of high-dose IR on global gene expression during bone marrow recovery remains unknown.
  
  
  METHODS
  Microarray analysis was used to identify differentially expressed genes that are likely to be critical for bone marrow recovery. Multiple bioinformatics analyses were conducted to identify key hub genes, pathways and biological processes.
  
  
  RESULTS
  1) We identified 1302 differentially expressed genes in murine bone marrow at 3, 7, 11 and 21 days after irradiation. Eleven of these genes are known to be HSC self-renewal associated genes, including Adipoq, Ccl3, Ccnd1, Ccnd2, Cdkn1a, Cxcl12, Junb, Pten, Tal1, Thy1 and Tnf; 2) These 1302 differentially expressed genes function in multiple biological processes of immunity, including hematopoiesis and response to stimuli, and cellular processes including cell proliferation, differentiation, adhesion and signaling; 3) Dynamic Gene Network analysis identified a subgroup of 25 core genes that participate in immune response, regulation of transcription and nucleosome assembly; 4) A comparison of our data with known irradiation-related genes extracted from literature showed 42 genes that matched the results of our microarray analysis, thus demonstrated consistency between studies; 5) Protein-protein interaction network and pathway analyses indicated several essential protein-protein interactions and signaling pathways, including focal adhesion and several immune-related signaling pathways.
  
  
  CONCLUSIONS
  Comparisons to other gene array datasets indicate that global gene expression profiles of irradiation damaged bone marrow show significant differences between injury and recovery phases. Our data suggest that immune response (including hematopoiesis) can be considered as a critical biological process in bone marrow recovery. Several critical hub genes that are key members of significant pathways or gene networks were identified by our comprehensive analysis.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Zejian
authors.initials: Z
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.forename: Xudong
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D019295:Computational Biology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps / Q000502:physiology; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects