{"owner": "ArrayExpress Uploader", "ownerprofile_id": "arrayexpress_sid", "species": "mouse", "factors": [{"GSE17250GSM432115": {}}, {"GSE17250GSM432116": {}}, {"GSE17250GSM432117": {}}, {"GSE17250GSM432118": {}}, {"GSE17250GSM432119": {}}, {"GSE17250GSM432120": {}}, {"GSE17250GSM432121": {}}, {"GSE17250GSM432122": {}}, {"GSE17250GSM432123": {}}, {"GSE17250GSM432124": {}}, {"GSE17250GSM432125": {}}, {"GSE17250GSM432126": {}}, {"GSE17250GSM432127": {}}, {"GSE17250GSM432128": {}}, {"GSE17250GSM432129": {}}, {"GSE17250GSM432130": {}}, {"GSE17250GSM432131": {}}, {"GSE17250GSM432132": {}}, {"GSE17250GSM432133": {}}, {"GSE17250GSM432134": {}}, {"GSE17250GSM432135": {}}, {"GSE17250GSM432136": {}}, {"GSE17250GSM432137": {}}, {"GSE17250GSM432138": {}}], "id": 5764, "pop_total": 0, "platform": 6, "summary_wrapped": "Studies in mice have shown that PPAR\u03b1 is an important regulator of hepatic lipid metabolism and the acute phase response. However, little...", "geo_gse_id": "E-GEOD-17250", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 0, "sample_count": 24, "tags": ["collagen", "insulin", "lipid", "liver", "serum"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "transcription-profiling-of-human-and-mouse-hepatoc", "geo_id_plat": "E-GEOD-17250_A-AFFY-45", "name": "Transcription profiling of human and mouse hepatocytes to perform a comparative analysis of gene regulation by the transcription factor PPARI?_mouse", "created": "Nov.11, 2014", "summary": "Studies in mice have shown that PPAR\u03b1 is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR\u03b1 in human liver. Here we set out to compare the function of PPAR\u03b1 in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR\u03b1 agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR\u03b1 expression was similar in human and mouse hepatocytes. Depending on  species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR\u03b1 in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR\u03b1 targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR\u03b1 in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR\u03b1 targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR\u03b1 activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR\u03b1 as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR\u03b1 regulates a mostly divergent set of genes in mouse and human hepatocytes. Experiment Overall Design: Primary hepatocytes from 6 mice from 6 different strains were treated with the PPAR\u03b1 agonist Wy14643 for 6 and 24 hours, and gene expression profiling was performed using Affymetrix GeneChips.  Mouse primary hepatocytes were isolated by two-step collagenase perfusion from 6 different strains of mouse; NMRI, SV129, FVB, DBA, BALB/C and C57BL/6J.   Cells were plated on collagen-coated six-well plates. Viability was determined by Trypan Blue exclusion, and was at least 75%. Hepatocytes were suspended in William's E medium (Lonza Bioscience, Verviers, Belgium) supplemented with 10% (v/v) fetal calf serum, 20 m-units/mL insulin, 10 nM dexamethasone, 100 U/mL penicillin, 100 \u03bcg/mL of streptomycin, 0.25 \u03bcg/mL fungizone and 50 \u03bcg/mL gentamycin. After four hours the medium was discarded and replaced with fresh medium. The next day, cells were incubated in fresh medium in the presence or absence of Wy14643 (10 microM) dissolved in DMSO for 6 and 24 hours, followed by RNA isolation. A 5-fold lower concentration of Wy14643 was used in mouse primary hepatocytes to take into account the higher affinity of Wy14643 for mouse PPAR\u03b1 compared to human PPAR\u03b1.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-17250", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-17250/samples/"}