Whole genome analysis of Sertoli cell gene expression by retinoblastoma-1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE17904 | GEO | 2009/09/02
SECONDARY ACCESSION(S): PRJNA119973
REPOSITORIES: GEO
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Project description:Gene expression profiling study of Sertoli cells (Sc)-specific Retinoblastoma (Rb) knockout (KO) mice. We generated a Sc-specific Rb knockout (Sc-RbKO) line and characterised its testicular phenotype. Sc-RbKO showed a progressive germ cell depletion leading to infertility and Sc dysfunction. We observed that up to 10 days old, Sc-RbKO mice present a phenotype similar to that of their WT siblings. This age was choosen to study the gene expression changes that would eventually lead to the described phenotypical changes. Sc-RbKO testis gene expression was compared to WT and to Sc-Rb+/- samples. Our Microarray results show changes of many genes involved in cell cycle control, DNA repair, apoptosis and misregulation of genes that may be important for proper Sertoli cell function such as tight junction formation, cell membrane and tissue remodeling. Total RNA extracted from 12 testicular samples, 5 controls, 3 hetorozygotes and 4 homozygotes.
2011-01-01 | E-GEOD-22234 | biostudies-arrayexpress
Project description:Gene expression profiling study of Sertoli cells (Sc)-specific Retinoblastoma (Rb) knockout (KO) mice. We generated a Sc-specific Rb knockout (Sc-RbKO) line and characterised its testicular phenotype. Sc-RbKO showed a progressive germ cell depletion leading to infertility and Sc dysfunction. We observed that up to 10 days old, Sc-RbKO mice present a phenotype similar to that of their WT siblings. This age was choosen to study the gene expression changes that would eventually lead to the described phenotypical changes. Sc-RbKO testis gene expression was compared to WT and to Sc-Rb+/- samples. Our Microarray results show changes of many genes involved in cell cycle control, DNA repair, apoptosis and misregulation of genes that may be important for proper Sertoli cell function such as tight junction formation, cell membrane and tissue remodeling.
2011-01-01 | GSE22234 | GEO
Project description:Human embryonic stem cells (hESCs) provide a platform for understanding mechanisms underlying diseases and finding ways to treat them. Trilateral retinoblastoma (TRb) is a condition in which retinoblastoma, the most common congenital intraocular malignancy, is associated with an intracranial neural tumor. This mostly fatal disease is caused by biallelic inactivation of the retinoblastoma-1 (RB1) gene, transcribing pRB. Using CRISPR-Cas9 we generated RB1-null hESCs, an embryonic lethal condition. These cells display distinct gene expression patterns with alterations in pRB targets, and mitochondrial phenotypes similar to those of poorly differentiated retinoblastomas. RB1–/– hESC produce extremely large teratomas, with neural expansions similar to those of TRb tumors. Analysis of these tumors revealed a potentially novel role of pRB in ectoderm differentiation, acting through ZEB1. Lastly, RB1–/– cells are significantly sensitive to carboplatin, a chemotherapy used to treat TRb, suggesting our model can be used to screen novel treatments for the disease.
2017-04-09 | GSE84504 | GEO
Project description:Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. To develop a laboratory model of human retinoblastoma formation, we made induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. After 45 days in culture, the retinal organoids were dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs had molecular, cellular and genomic features indistinguishable from human retinoblastomas.
2021-05-11 | GSE174201 | GEO
Project description:Background Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1-/- retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling. Methods Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data. Findings RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1-/- tumors seemed more dichotomous, differences within the RB1-/- tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared to tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations. Interpretation Molecular, clinical and histopathological differences between RB1-/- tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression. Fresh frozen material from 76 primary human retinoblastoma samples were profiled with Affymetrix human genome u133 plus 2.0 PM microarray
2015-07-01 | E-GEOD-59983 | biostudies-arrayexpress
Project description:Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. To develop a laboratory model of human retinoblastoma formation, we made induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. After 45 days in culture, the retinal organoids were dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs had molecular, cellular and genomic features indistinguishable from human retinoblastomas.
2021-05-11 | GSE174200 | GEO
Project description:carboplatin resistance retinoblastoma cell lines (Weri-RB1/CRP) transfect SNHG1-specific shSNHG1 to knockdown SNHG1 and analysis differential gene in Weri-RB1/CRP
2021-04-10 | GSE171455 | GEO
Project description:<p>Retinoblastoma is a pediatric cancer of the developing retina. All retinoblastomas are believed to initiate with biallelic inactivation of the RB1 gene. To identify subsequent genetic lesions in retinoblastoma, we performed whole genome sequencing of tumor and normal DNA of 4 children with retinoblastoma and one matched orthotopic xenograft. Both alleles of RB1 were inactivated in the tumor samples. 3 of the patients had sporadic retinoblastoma and one patient had inherited retinoblastoma. Overall, there were few single nucleotide changes in coding regions of the genome and some of the tumors had few chromosomal lesions. There were very few new genetic lesions in the xenograft compared to the primary tumor. These data suggest that the genome in retinoblastoma is more stable than previously believed and there are relatively few recurrent genetic lesions in known cancer pathways other than the RB1 pathway.</p>
| phs000352 | dbGaP
Project description:Retinoblastoma (Rb), the most prevalent intraocular malignant tumor in children with global survival rate less than 30%, is mainly caused by the deficiency of the tumor suppressor RB1. A line of evidence have shown that local inflammation and immune escape play important roles in the occurrence of Rb, however the underlying mechanism remains unclear. We hypothesize that the unique neuroimmune cell type, retinal microglia, has a vital role in the Rb pathogenesis. In this study, we differentiated microglia cells (iMGs) from established induced pluripotent stem cells (iPSCs) derived from a retinoblastoma patient with the defined RB1 mutations. We investigated the function of RB1 in innate immune response of microglia and found that the expression of interleukins and chemokines, especially interleukin 6 and TNF-α, were highly upregulated in LPS-stimulated RB1 deficient iMGs, which enhanced innate immune responses and created a pro-inflammation environment. These findings demonstrated that RB1 is indispensable to maintain microglia function in innate immunity and its deficiency leads to enhanced inflammation responses, which may accelerate tumor growth and malignancy. This study provides new insights for pathological mechanism and immunotherapeutic target of retinoblastoma.
2022-12-31 | GSE212248 | GEO
Project description:Retinoblastoma is the most common intraocular cancer of infancy and childhood, with an incidence of one case per 15,000 - 20,000 live births. An early event in retinoblastoma genesis is a functional loss of both alleles of the RB1 gene. However, other genes are likely to be involved in the development of this cancer. In this study we sought to build a comprehensive molecular portrait of this cancer by performing transcriptomic, methylomic, genomic profiling of primary retinoblastoma samples. Most of the patients whose tumors were studied had received no treatment prior to surgical enucleation.
2021-07-06 | GSE58783 | GEO