Sleep and affective behaviors are highly interrelated phenotypes, commonly altered in a variety of neuropsychiatric diseases, including major depressive disorder (MDD). To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions, including the frontal cortex, hippocampus, thalamus, and hypothalamus. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Utilizing publicly available transcriptomic datasets collected from sleep-deprived mice and major depressive disorder (MDD) patients, we identified three cortical gene networks altered by sleep/wake changes and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression.
Sex, Specimen part
View SamplesGene expression analysis was performed from microdissected small and big HRS cells, which were taken from smears of the Hodgkin cell lines
Small and big Hodgkin-Reed-Sternberg cells of Hodgkin lymphoma cell lines L-428 and L-1236 lack consistent differences in gene expression profiles and are capable to reconstitute each other.
Specimen part
View SamplesNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior. Mechanisms involved in the reduced tumor cell proliferation included a downregulation of MYC and its target genes. Lack of MYC expression was also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD-L1 was upregulated in tumor cells after coculture with T cells or monocytes and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data provide new insights into the pathogenesis of LP-DLBCL and a concrete explanation of the relatively low tumor cell content. Moreover, our results suggest that treatment of these patients with checkpoint inhibitors may enhance an already ongoing host response in these patients.
A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma.
Specimen part
View SamplesNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL
A strong host response and lack of MYC expression are characteristic for diffuse large B cell lymphoma transformed from nodular lymphocyte predominant Hodgkin lymphoma.
Specimen part, Cell line
View SamplesTumor cells were microdissected from frozen sections of NLPHL and THRLBCL. RNA was amplified using the NUGEN WT-Ovation-One-direct-Kit. Samples were compared to tonsilar germinal center CD77 B cells.
Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?
Specimen part
View SamplesHodgkin's lymphoma (HL) is one of the most frequent hematological malignancies. Due to its extraordinary composition, few tumor cells surrounded by a reactive infiltrate, HL can be seen as an ideal model system for research focusing on tumor immunology. In fact, the tumor cells of HL, so called Hodgkin/Reed-Sternberg (HRS) cells attract CD4+ T cells, which then build rosettes with the HRS cells. HRS cells further modulate the tumor microenvironment with the help of CD4+ T cells to avoid tumor rejection. Here, we mimicked this scenario using compatible CD4+ T cells receiveing data of profound interactions for the first time, as former studies were performed with allogeneic donors. Finally, we genetically retargeted compatible CD4+ T cells to kill HRS cells.
Tumor-infiltrating HLA-matched CD4(+) T cells retargeted against Hodgkin and Reed-Sternberg cells.
Cell line
View SamplesFrom the transcriptomics analysis, this study focused on the genes expressed in PGCs during germline development in early embryogenesis of chickens.
MicroRNA-mediated posttranscriptional regulation is required for maintaining undifferentiated properties of blastoderm and primordial germ cells in chickens.
Specimen part
View SamplesThe present investigation was to identify the signaling and metabolic pathways of expressed genes by microarray comparison between Primordial Germ Cells (PGCs) and their somatic counterpart, chicken embryonic fibroblasts (CEFs).
Gene pathways and cell cycle-related genes in cultured avian primordial germ cells.
Specimen part
View SamplesHearts Lacking Caveolin-1 Develop Hypertrophy with Normal Cardiac Substrate Metabolism
Hearts lacking caveolin-1 develop hypertrophy with normal cardiac substrate metabolism.
No sample metadata fields
View SamplesComprehensive RNA-seq experiments in control and PRMT5 and WDR77 shRNA infected cells delineate the role of PRMT5/WDR77 complex in promoting breast cancer oncogenesis Overall design: RNA-seq was used to measure gene expression levels in scrambled control, PRMT5 and WDR77 short hairpin RNA (shRNA) infected human breast cancer cells
The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer.
No sample metadata fields
View Samples