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GSE62322
Homo sapiens
112 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Diet-induced obesity is characterized by macrophage (MF) infiltration and low-grade chronic inflammation in white adipose tissue (WAT) leading to insulin resistance. WAT MF are highly heterogeneous in their origin, patterns of gene expression and activities: unlike infiltrating monocyte-derived MF that promote inflammation and metabolic dysfunction, tissue-resident WAT MF originally described as ‘M2’ are phenotypically anti-inflammatory and counteract obesity and insulin resistance. Despite the critical role of the balance between these MF populations in metabolic homeostasis, the molecular mechanisms and key players that establish the resident MF transcription program are poorly understood. We recently reported that glucocorticoid receptor (GR)-interacting protein (GRIP)1 - a nuclear receptor coactivator - cooperates with GR to repress transcription of inflammatory genes. Here, using mice conditionally lacking GRIP1 in MF (cKO), we show that GRIP1 promotes MF polarization in response to IL4 (M2(IL4)) via a nuclear receptor-independent pathway by serving as a coactivator for Kruppel-like factor (KLF)4 – a critical driver of tissue MF differentiation. Interestingly, in vivo, GRIP1 cKO mice challenged with high-fat diet develop massive MF infiltration and chronic inflammation in WAT and liver, fatty livers, hyperglycemia, hyperinsulinemia and glucose intolerance consistent with metabolic syndrome phenotype. Together, our findings identify GRIP1 as a critical regulator of immunometabolism, which relies on distinct transcriptional mechanisms to coordinate the balance between MF populations in vivo thereby protecting mice from obesity-induced metabolic disease. Overall design: 1. Examination of IL4 induced transcriptome in in vitro differentiated primary bone marrow-derived macrophages. 2. Examination of macrophage transcriptome in macrophages isolated from the white adipose tissue of the WT and GRIP1(cKO) conditional KO animals
Publication Title
The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 4000
Description
Germline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients. Overall design: RNA-sequencing of 12 Smarcb1-deficient mouse cranial nerves and meninges tumors
Publication Title
Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Despite the well-established role of the frontal and posterior peri-sylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in human brain. We performed a genome-wide analysis of human cerebral patterning during mid-gestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed (DE) between superior temporal gyrus (STG) and the remaining cerebral cortex (CTX). GO categories representing transcription factors were enriched in STG, while cell-adhesion and extracellular matrix molecules, were enriched in the other cortical regions. Q-PCR or in situ hybridization were performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LMO4), a gene known to be involved in the asymmetric pattering of the peri-sylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin Associated Protein-Like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy and language delay, showed a remarkable pattern of anterior enriched expression in cortical regions important for human higher cognition. Importantly, a similar pattern was not observed in the mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and disorders that disrupt them.
Publication Title
Genome-wide analyses of human perisylvian cerebral cortical patterning.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina Genome Analyzer
Description
Regional identity of several kind of human neural stem cells were assessed by RNA-Seq Overall design: We compared whole transcriptome of human fetal spinal cord, fetal brain, fetal spinal cord derived NSCs, H9-derived NSCs, H9-derived spinal cord NSCs, and UCSF4-derived spinal cord NSCs
Publication Title
Generation and post-injury integration of human spinal cord neural stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To determine the modulation of gene expression of C57BL/6 and DBA/2 BMDLs in the presence of living intracellular Leishmania amazonensis amastigotes
Publication Title
Distinct transcriptional signatures of bone marrow-derived C57BL/6 and DBA/2 dendritic leucocytes hosting live Leishmania amazonensis amastigotes.
Sample Metadata Fields
Specimen part
View Samples