ACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushings disease (CD)] is the most common cause of endogenous Cushings syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF- and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas.
Sex, Specimen part, Disease
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Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesGlobal microarray (HG U133 Plus 2.0) was used to investigate the effects of resistance exercise and resistance training on the skeletal muscle transcriptome profile of 28 young and old adults. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part, Time
View SamplesGlobal microarray (HG U133 Plus 2.0) was used for the first time to investigate the effects of resistance exercise on the transcriptome in slow-twitch myosin heavy chain (MHC) I and fast-twitch MHC IIa muscle fibers of young and old women. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part, Subject, Time
View SamplesGlobal microarray (HG U133 Plus 2.0) was used to investigate the basal level skeletal muscle transcriptome profile of young and old adults. One vastus lateralis muscle biopsy was obtained in the basal state from 36 different subjects.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part
View SamplesWe report an applicaton of small RNA sequencing using high throughput next generation sequencing to identify the small RNA content of cell lines. By sequencing over 30 million reads we could identify a new class of small RNAs previousy observed with tiling arrays and mapping to promoter regions of coding genes. We also identified a large number of small RNAs corresponding to internal exons of coding genes. By using different enzymatic treatments and immunoprecipitation experiments, we have determined that both the promoter associated small RNAs as well as ones within the body of the genes bear 5'' cap structures. Overall design: Examination of the expression of small RNAs (<200nt).
Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs.
No sample metadata fields
View SamplesGM-CSF receptor- deficient (Csf2rb/ or KO) mice develop a lung disease identical to hereditary pulmonary alveolar proteinosis (hPAP) in humans with recessive CSF2RA or CSF2RB mutations that impair GM-CSF receptor function. We performed pulmonary macrophage transplantation (PMT) of bone marrow derived macrophages (BMDMs) without myeloablation in Csf2rb/mice. BMDMs were administered by endotracheal instillation into 2 month-old Csf2rb/ mice. Results demonstrated that PMT therapeutic of hPAP in Csf2rb/ mice was highly efficacious and durable. Alveolar macrophages were isolated by bronchoalveolar lavage one year after administration subjected to microarray analysis to determine the effects of PMT therapy on the global gene expression profile.
Pulmonary macrophage transplantation therapy.
Specimen part, Treatment
View SamplesGene expression analysis of wid type and Lmnb1-/- epicardial cells Overall design: Total RNA was isolated from wild type and Lmnb1-/- epicardial explants and subject ot sequencing on the Illumina platform
Lamin-B1 contributes to the proper timing of epicardial cell migration and function during embryonic heart development.
Cell line, Subject
View SamplesViral infection can dramatically alter a cell''s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in production of viral gene transcripts -- viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells. Overall design: Dataset consists of a total of five single-cell datasets generated using the 10x Genomics Chromium Single Cell 3'' Solution platform. All samples were generated from a tissue culture infection model using A549 cells from ATCC and Influenza A/WSN/1933 virus. Uninfected control sample identically processed. Infected samples were generated from cells infected for 6, 8, and 10 hours with a single replicate at 8 hours.
Extreme heterogeneity of influenza virus infection in single cells.
Cell line, Subject
View SamplesFACS sorted TPCs (CD24HighCD44LowEpCAMHigh) and non-TPCs (CD24Low, CD24HighCD44High, and CD24HighCD44LowEpCAMLow) from mouse primary SCLC tumors
Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer.
Specimen part
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