Human hepatic stem cells transplanted into a fulminant hepatic failure Alb-TRECK/SCID mouse model exhibit liver reconstitution and drug metabolism capabilities
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62933 | GEO | 2015/03/04
SECONDARY ACCESSION(S): PRJNA266230
REPOSITORIES: GEO
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Project description:Comparison of liver developmental gene expression of human hepatic stem cells (HpSCs), human primary fetal liver cells (FLCs), human adult hepatocyte (AH) and HpSCs or FLC-derived humanized liver. 8 Samples were analyzed
2015-03-04 | E-GEOD-62933 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4414454 | biostudies-literature
Project description:Previous studies have established that fetal Leydig cells (FLCs) and adult Leydig cells (ALCs) show distinct functional characteristics. However, the lineage relationship between FLCs and ALCs has not been clarified yet. Here we reveal that a subset of FLCs dedifferentiate at fetal stages to give rise to ALCs at the pubertal stage. Moreover, the dedifferentiated cells contribute to the peritubular myoid cells and vascular pericyte populations in the neonatal testis, and these non-steroidogenic cells serve as potential ALC stem cells. We generated FLC lineage-specific Nr5a1 (Ad4BP/SF-1) gene disrupted mice and mice lacking the fetal Leydig enhancer (FLE) of the Nr5a1 gene. Phenotypes of these mice support the conclusion that most of the ALCs arise from dedifferentiated FLCs, and that the FLE of Nr5a1 gene is essential for both initial FLC differentiation and pubertal ALC redifferentiation.
2018-11-26 | GSE122886 | GEO
Project description:Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer usually developed in non-cirrhotic livers of children and young adults with unknown etiology. Treatment is limited to surgical intervention. To date, molecular pathogenesis of FLC has been poorly characterized. A cohort of FLCs was analyzed through SNP-array. GISTIC algorithm identified chromosomal aberrations.
2015-02-12 | GSE59443 | GEO
Project description:Background & Aims: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer usually developed in non-cirrhotic livers of children and young adults with unknown etiology. Treatment is limited to surgical intervention. To date, molecular pathogenesis of FLC has been poorly characterized. Herein, we aim to provide an integrative genomic analysis from a large series of FLC patients. Methods: A clinically annotated cohort of 77 FLCs was analyzed through wholetranscriptome, SNP-array and whole-exome sequencing. Non-negative matrix factorization was performed for class discovery, and GSEA, NTP, IPA and immunohistochemistry for functional annotation. GISTIC algorithm identified chromosomal aberrations; Mutect and VarScan2, somatic mutations, and Random survival forest the prognostic signature, validated in an independent cohort. Results: Unsupervised gene expression clustering revealed 3 robust molecular classes: Proliferation-51%, enriched with liver cancer proliferation signatures and mTOR signaling activation, Inflammation-26%, with pro-inflammatory cytokines signatures, and Unannotated-23%, with non-liver-related cancer signatures. Neuroendocrine genes and cholangiocyte and hepatocyte histological markers were present in all classes. FLC showed few copy number variations, being the most frequent: focal amplification at 8q24.3(12.5%), and deletions at 19p13(28%) and 22q13.32(25%). DNAJB1-PRKACA fusion transcript was observed in 79% of cases. FLC tumors had 32 damaging mutations on average, affecting uncommon genes in liver neoplasms (BRCA2, U2AF1). An 8-gene prognostic signature predicted survival in FLC patients. Conclusions: FLC genomic analysis reveals a unique molecular portrait characterized by uncommon damaging mutations and chromosomal aberrations, and a highly prevalent fusion protein. Three molecular classes, including Proliferation and Inflammation, define the biological behavior. Prognostic signature will allow better patient stratification. Gene-expression profiles of fresh frozen human fibrolamellar hepatocellular carcinoma
2015-02-12 | E-GEOD-57726 | biostudies-arrayexpress
Project description:Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer usually developed in non-cirrhotic livers of children and young adults with unknown etiology. Treatment is limited to surgical intervention. To date, molecular pathogenesis of FLC has been poorly characterized. A cohort of FLCs was analyzed through SNP-array. GISTIC algorithm identified chromosomal aberrations. FLC tumors corresponding to 25 different patients. In all cases, tumor and corresponding non-tumor samples were frozen (-80°C) after hepatic resection at diagnosis. Comparative Genomic Hybridization analysis was done using Illumina HumanHap370CNV Genotyping BeadChip SNP array
2015-02-12 | E-GEOD-59443 | biostudies-arrayexpress
Project description:Background & Aims: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer usually developed in non-cirrhotic livers of children and young adults with unknown etiology. Treatment is limited to surgical intervention. To date, molecular pathogenesis of FLC has been poorly characterized. Herein, we aim to provide an integrative genomic analysis from a large series of FLC patients. Methods: A clinically annotated cohort of 77 FLCs was analyzed through whole transcriptome, SNP-array and whole-exome sequencing. Non-negative matrix factorization was performed for class discovery, and GSEA, NTP, IPA and immunohistochemistry for functional annotation. GISTIC algorithm identified chromosomal aberrations; Mutect and VarScan2, somatic mutations, and Random survival forest the prognostic signature, validated in an independent cohort. Results: Unsupervised gene expression clustering revealed 3 robust molecular classes: Proliferation-51%, enriched with liver cancer proliferation signatures and mTOR signaling activation, Inflammation-26%, with pro-inflammatory cytokines signatures, and Unannotated-23%, with non-liver-related cancer signatures. Neuroendocrine genes and cholangiocyte and hepatocyte histological markers were present in all classes. FLC showed few copy number variations, being the most frequent: focal amplification at 8q24.3(12.5%), and deletions at 19p13(28%) and 22q13.32(25%). DNAJB1-PRKACA fusion transcript was observed in 79% of cases. FLC tumors had 32 damaging mutations on average, affecting uncommon genes in liver neoplasms (BRCA2, U2AF1). An 8-gene prognostic signature predicted survival in FLC patients. Conclusions: FLC genomic analysis reveals a unique molecular portrait characterized by uncommon damaging mutations and chromosomal aberrations, and a highly prevalent fusion protein. Three molecular classes, including Proliferation and Inflammation, define the biological behavior. Prognostic signature will allow better patient stratification. Gene-expression profiles of formalin-fixed, paraffin-embedded human fibrolamellar hepatocellular carcinoma
2015-02-12 | E-GEOD-57725 | biostudies-arrayexpress
Project description:Background & Aims: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer usually developed in non-cirrhotic livers of children and young adults with unknown etiology. Treatment is limited to surgical intervention. To date, molecular pathogenesis of FLC has been poorly characterized. Herein, we aim to provide an integrative genomic analysis from a large series of FLC patients. Methods: A clinically annotated cohort of 77 FLCs was analyzed through wholetranscriptome, SNP-array and whole-exome sequencing. Non-negative matrix factorization was performed for class discovery, and GSEA, NTP, IPA and immunohistochemistry for functional annotation. GISTIC algorithm identified chromosomal aberrations; Mutect and VarScan2, somatic mutations, and Random survival forest the prognostic signature, validated in an independent cohort. Results: Unsupervised gene expression clustering revealed 3 robust molecular classes: Proliferation-51%, enriched with liver cancer proliferation signatures and mTOR signaling activation, Inflammation-26%, with pro-inflammatory cytokines signatures, and Unannotated-23%, with non-liver-related cancer signatures. Neuroendocrine genes and cholangiocyte and hepatocyte histological markers were present in all classes. FLC showed few copy number variations, being the most frequent: focal amplification at 8q24.3(12.5%), and deletions at 19p13(28%) and 22q13.32(25%). DNAJB1-PRKACA fusion transcript was observed in 79% of cases. FLC tumors had 32 damaging mutations on average, affecting uncommon genes in liver neoplasms (BRCA2, U2AF1). An 8-gene prognostic signature predicted survival in FLC patients. Conclusions: FLC genomic analysis reveals a unique molecular portrait characterized by uncommon damaging mutations and chromosomal aberrations, and a highly prevalent fusion protein. Three molecular classes, including Proliferation and Inflammation, define the biological behavior. Prognostic signature will allow better patient stratification.
2015-02-12 | GSE57726 | GEO
Project description:Background & Aims: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer usually developed in non-cirrhotic livers of children and young adults with unknown etiology. Treatment is limited to surgical intervention. To date, molecular pathogenesis of FLC has been poorly characterized. Herein, we aim to provide an integrative genomic analysis from a large series of FLC patients. Methods: A clinically annotated cohort of 77 FLCs was analyzed through whole transcriptome, SNP-array and whole-exome sequencing. Non-negative matrix factorization was performed for class discovery, and GSEA, NTP, IPA and immunohistochemistry for functional annotation. GISTIC algorithm identified chromosomal aberrations; Mutect and VarScan2, somatic mutations, and Random survival forest the prognostic signature, validated in an independent cohort. Results: Unsupervised gene expression clustering revealed 3 robust molecular classes: Proliferation-51%, enriched with liver cancer proliferation signatures and mTOR signaling activation, Inflammation-26%, with pro-inflammatory cytokines signatures, and Unannotated-23%, with non-liver-related cancer signatures. Neuroendocrine genes and cholangiocyte and hepatocyte histological markers were present in all classes. FLC showed few copy number variations, being the most frequent: focal amplification at 8q24.3(12.5%), and deletions at 19p13(28%) and 22q13.32(25%). DNAJB1-PRKACA fusion transcript was observed in 79% of cases. FLC tumors had 32 damaging mutations on average, affecting uncommon genes in liver neoplasms (BRCA2, U2AF1). An 8-gene prognostic signature predicted survival in FLC patients. Conclusions: FLC genomic analysis reveals a unique molecular portrait characterized by uncommon damaging mutations and chromosomal aberrations, and a highly prevalent fusion protein. Three molecular classes, including Proliferation and Inflammation, define the biological behavior. Prognostic signature will allow better patient stratification.
2015-02-12 | GSE57725 | GEO
Project description:Fibrolamellar carcinoma (FLC) is a rare liver cancer. Here we characterized the small RNA expression landscape of primary FLC, a FLC patient-derived xenograft model, and normal maturational liver lineage stages
2019-03-07 | GSE114974 | GEO