Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell-fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 in retinal development and retinoblastoma by using molecular and cellular approaches. Brg1 regulated retinal size by controlling cell cycle length, cell cycle exit, and cell survival during development. Brg1 was not required for cell-fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death, and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, thereby making them more susceptible to retinoblastoma. ChIP-seq analysis provided insight into the underlying molecular mechanisms of these complex Brg1-regulated cellular processes during retinal development.
Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma.
Specimen part
View SamplesEpigenetic mechanisms play an important role in the cellular development and maintenance of cellular homeostasis. Any alteration of epigenetic mechanisms via the changes in DNA methylation and histone modification may lead to various diseases including cancer. The differential expression of histone modifiers has been observed in various malignancies.
PAK2-c-Myc-PKM2 axis plays an essential role in head and neck oncogenesis via regulating Warburg effect.
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View SamplesTp80 is a novel antiviral compound. Antiviral mechanism of Tp80 is the inhibition of the viral genome replication through the recoverly of GPx2 expression downregulated by HCV infection.
Retinoid derivative Tp80 exhibits anti-hepatitis C virus activity through restoration of GI-GPx expression.
Specimen part, Cell line, Treatment
View SamplesThe formation and execution of a productive immune response requires, among many things, the maturation of competent T cells and a robust change in cellular activity upon antigen challenge. Such changes in cellular function require regulated alterations of protein expression. Much work has previously gone into defining the transcriptional changes that regulate protein expression during T cell development and antigen stimulation. Here we describe a parallel pathway of gene regulation that occurs during T cell stimulation, namely alternative splicing. Specifically, we use RNA-Seq to identify 178 exons in 168 genes that exhibit robust changes in inclusion in response to a stimulation of a human T cell line. Interestingly, these signal-responsive genes are enriched for functions related to immune response including, cell trafficking, inflammatory and immune response, immunologic disease and several cell signaling pathways. The vast majority of these genes also exhibit different isoform expression in naive and activated primary T cells. Comparison of the responsiveness of splicing to various stimuli in the cultured and primary T cells reveal important insight into the diversity of signaling pathways that control splicing. Using this data we are able to classify signal-responsive exons into at least three distinct networks. Importantly, we find that each regulatory network is characterized by distinct sequence hallmarks, further suggesting independent regulatory mechanisms. Overall design: We utilize high-throughput RNA sequencing (RNA-Seq) to investigate global changes in alternative splicing in a cultured T cell line and in primary human T cells. We identify 178 genes that are predicted to exhibit robust signal-induced changes in isoform expression in cultured T cells.
Alternative splicing networks regulated by signaling in human T cells.
Specimen part, Subject
View SamplesDuring mammalian gastrulation, pluripotent epiblast stem cells migrate through the primitive streak to form the multipotent progenitors of the mesoderm and endoderm germ layers. Msgn1 is a bHLH transcription factor and is a direct target gene of the Wnt/bcatenin signaling pathway. Msgn1 is expressed in the mesodermal compartment of the primitive streak and is necessary for the proper development of the mesoderm. Msgn1 mutants show defects in somitogenesis leading to a lack of trunk skeletal muscles, vertebra and ribs.
The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
Specimen part, Treatment
View SamplesThe goal of this project was to elucidate the target genes and transcriptional networks activated by Wnt3a during gastrulation, a complex morphogenetic process in which the embryonic germ layers are formed and the vertebrate body plan is established.
The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
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View SamplesExpression profiling of L4 and L5 Dorsal Root Ganglion (DRG) in the spinal nerve ligation model of neuropathic pain. The goal of the study was to identify genes involved in neuropathic pain
Dynamic changes in the microRNA expression profile reveal multiple regulatory mechanisms in the spinal nerve ligation model of neuropathic pain.
Sex, Specimen part
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