Global 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 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 SamplesSchwann cell remyelination defects impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms that mediate remyelination block remain elusive. Upon small-molecule epigenetic screening, we identified HDAC3, a histone-modifying enzyme, as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 markedly enhances myelin growth and regeneration, and improves functional recovery after peripheral nerve injury. HDAC3 antagonizes myelinogenic neuregulin/PI3K/AKT signaling axis. Moreover, genome-wide profiling analyses reveal that HDAC3 represses pro-myelinating programs through epigenetic silencing, while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann-cell-specific deletion of either Hdac3 or Tead4 results in a profound increase in myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3-TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair. Overall design: 4 RNA-Seq samples from P6 sciatic nerves of Ctrl and Hdac3-cKO mice (Cnpcre-Ctrl, Cnpcre-cKO, Dhhcre-Ctrl, Dhhcre-cKO)
A histone deacetylase 3-dependent pathway delimits peripheral myelin growth and functional regeneration.
Specimen part, Subject
View SamplesIn the present study, we investigated the importance of histone deacetylase 6 (HDAC6) for glucocorticoid receptor (GR) mediated effects on glucose metabolism, and its potential as a therapeutic target for the prevention of glucocorticoid (GC)-induced diabetes. Dexamethasone (dex)-induced hepatic glucose output and GR translocation were analysed in wildtype (wt) and HDAC6-deficient (HDAC6ko) mice. The effect of the specific HDAC6-inhibitor tubacin was analysed in-vitro. Wt and HDAC6ko mice were subjected to 3 weeks dex treatment before analysis of glucose and insulin tolerance. HDAC6ko mice showed impaired dex-induced hepatic GR translocation. Accordingly, dex induced expression of a large number of hepatic genes was significantly attenuated in mice lacking HDAC6 and by tubacin in-vitro. Glucose output of primary hepatocytes from HDAC6ko mice was diminished. A significant improvement of dex-induced whole-body glucose intolerance as well as insulin resistance in HDAC6ko mice compared to wt littermates was observed. The present study demonstrates that HDAC6 is an essential regulator of hepatic GC stimulated gluconeogenesis and impairment of whole body glucose metabolism through modification of GR nuclear translocation. Selective pharmacological inhibition of HDAC6 may provide a future therapeutic option against the pro-diabetogenic actions of GCs.
Histone deacetylase 6 (HDAC6) is an essential modifier of glucocorticoid-induced hepatic gluconeogenesis.
Sex, Specimen part, Treatment
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 SamplesThis SuperSeries is composed of the SubSeries listed below.
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 SamplesWe report RNA sequencing of single olfactory neurons from mouse olfactory epithelium in developmental progression from progenitors to precursors to immature neurons to mature neurons. Most mature neurons expressed only one of ~ 1000 odorant receptor genes (Olfrs) at high levels, whereas many immature neurons expressed low levels of multiple Olfrs. Overall design: Investigating expression of odorant receptors genes in mouse olfactory sensory neurons during development.
Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis.
Cell line, Subject
View SamplesTranscriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat. Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen. To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control. Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). Overall design: There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.
A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.
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