The graft response to transplantation: a gene expression profile analysis

2003 ◽  
Vol 15 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Kenneth Christopher ◽  
Thomas F. Mueller ◽  
Rachel DeFina ◽  
Yurong Liang ◽  
Jianhua Zhang ◽  
...  

Little is known regarding the graft response to transplantation injury. This study investigates the posttransplantation response of genes that are constitutively expressed in the heart. Constitutive heart and lymph node tissue-restricted gene expression was first analyzed with DNA microarrays. To demonstrate changes following transplantation in genes constitutively expressed in the heart, we performed vascularized murine heart transplants in allogeneic (BALB/c to B6), syngeneic (B6 to B6), and alymphoid (BALB/c-RAG2−/− to B6-RAG1−/−) experimental groups. Temporal induction of genes posttransplant relative to constitutive expression was evaluated with DNA microarrays. Dendrograms and self-organizing maps were generated to determine the dissimilarity between the experimental groups and to identify subsets of differentially expressed genes within the groups, respectively. Expression patterns of selected genes were confirmed by real-time PCR. Biological processes were assigned to genes induced posttransplant using the AnnBuilder package via the Gene Ontology Database. Post-transplant, a shift was noted in genes classified as defense, communication, and metabolism. Our results identify novel components of the graft response to transplantation injury and rejection.

Author(s):  
Rianne R. Campbell ◽  
Siwei Chen ◽  
Joy H. Beardwood ◽  
Alberto J. López ◽  
Lilyana V. Pham ◽  
...  

AbstractDuring the initial stages of drug use, cocaine-induced neuroadaptations within the ventral tegmental area (VTA) are critical for drug-associated cue learning and drug reinforcement processes. These neuroadaptations occur, in part, from alterations to the transcriptome. Although cocaine-induced transcriptional mechanisms within the VTA have been examined, various regimens and paradigms have been employed to examine candidate target genes. In order to identify key genes and biological processes regulating cocaine-induced processes, we employed genome-wide RNA-sequencing to analyze transcriptional profiles within the VTA from male mice that underwent one of four commonly used paradigms: acute home cage injections of cocaine, chronic home cage injections of cocaine, cocaine-conditioning, or intravenous-self administration of cocaine. We found that cocaine alters distinct sets of VTA genes within each exposure paradigm. Using behavioral measures from cocaine self-administering mice, we also found several genes whose expression patterns corelate with cocaine intake. In addition to overall gene expression levels, we identified several predicted upstream regulators of cocaine-induced transcription shared across all paradigms. Although distinct gene sets were altered across cocaine exposure paradigms, we found, from Gene Ontology (GO) term analysis, that biological processes important for energy regulation and synaptic plasticity were affected across all cocaine paradigms. Coexpression analysis also identified gene networks that are altered by cocaine. These data indicate that cocaine alters networks enriched with glial cell markers of the VTA that are involved in gene regulation and synaptic processes. Our analyses demonstrate that transcriptional changes within the VTA depend on the route, dose and context of cocaine exposure, and highlight several biological processes affected by cocaine. Overall, these findings provide a unique resource of gene expression data for future studies examining novel cocaine gene targets that regulate drug-associated behaviors.


2007 ◽  
Vol 21 (12) ◽  
pp. 3262-3271 ◽  
Author(s):  
Béatrice Jacquelin ◽  
Veronique Mayau ◽  
Guillaume Brysbaert ◽  
Béatrice Regnault ◽  
Ousmane M. Diop ◽  
...  

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