Genomic profiling of normal and regenerating liver in young and old mice
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Maria Ravo
PROVIDER: E-MTAB-3374 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Normal adult liver is uniquely capable of renewal; and repair after injury. Whether this response; represents simple hyperplasia of various liver elements; or requires recapitulation of the genetic program of; the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferationassociated genes. Consistent with these findings, realtime polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level, restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury. Experiment Overall Design: In order to elucidate the molecular similarities between regenerating and developing liver, we performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for targets at 0, 1, 2, 6, 12, 18, 24, 30, 48, and 72 hours after partial hepatectomy and at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc). Experiment Overall Design: Each experimental time point is represented by two separate samples, each consisting of at least 3 pooled tissues from different animals. For example, 6 hepatectomies were performed for the 1 hour post-hepatectomy time point. Time 0 is used as control.
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Project description:Previous reports suggest that outcome of cHL patients may be related to the tumor microenvironment, which in turn may be influenced by EBV infection. Gene profiling was used for further characterize the cHL microenvironment. A training set of 73 cHL tissue samples was profiled using Affymetrix DNA microarrays. Supervised analysis provided a gene signature separating EBV+ from EBV- cHL tissues, including genes characteristic of Th1 and antiviral response. Samples from patients with favourable outcome significantly overexpressed genes involved in the function of B-cells and plasmacytoid dendritic cells (pDCs), like BCL11A. A validation set of 146 cHL samples was analyzed using immunohistochemistry (IHC). Experiment Overall Design: A training set of 73 pre-treatment cHL tissue samples was profiled using Affymetrix DNA microarrays. They were collected at the time of diagnosis from 73 different cHL patients (including 10 children under the age of 15), who underwent lymph node surgical biopsy in several French haematological centres (Marseilles, Lille, Dijon, Nancy, Paris) belonging to the network of the Groupe d’Etude des Lymphomas de l’Adulte (GELA). Each patient (or parents for children) gave written informed consent. Samples were snap-frozen in liquid nitrogen within 30 minutes of removal. All cases were de novo reviewed by 2 hematopathologists (BC and LX) before analysis.
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