Precise regulation of stem cell self-renewal and differentiation properties is essential for tissue homeostasis. Using the adult Drosophila intestine to study molecular mechanisms controlling stem cell properties, we identify the gene split-ends (spen) in a genetic screen as a novel regulator of intestinal stem cell fate. Spen family genes encode conserved RNA recognition motif-containing proteins that are reported to have roles in RNA splicing and transcriptional regulation. We demonstrate that spen loss of function in intestinal stem cells results in an abnormal increase in the number of stem cell-like cells and that Spen acts to control early commitment events of the stem cells. Using two-color cell sorting of stem cells and their daughters, we characterize spen-dependent changes in RNA abundance and exon usage, and find potential key regulators downstream of spen. Our work identifies spen as an important regulator of adult stem cells in the Drosophila intestine, provides new insight to Spen-family protein functions, and may also shed light on Spen's mode of action in other developmental contexts. Overall design: Three biological replicates were sequenced per each 4 conditions
Spen limits intestinal stem cell self-renewal.
Sex, Age, Specimen part, Subject
View SamplesThe nuclear exosome performs critical functions in non-coding RNA processing, and in diverse surveillance functions including the quality control of mRNP formation, and in the removal of pervasive transcripts. Most non-coding RNAs and pervasive nascent transcripts are targeted by the Nrd1p-Nab3p-Sen1p (NNS) complex to terminate Pol II transcription coupled to nuclear exosome degradation or 3´-end trimming. Prior to nuclear exosome activity, the Trf4p-Air2p-Mtr4p polyadenylation complex adds an oligo-A tail to exosome substrates. Inactivating exosome activity stabilizes and lengthens these A-tails. We utilized high-throughput 3´-end poly(A)+ sequencing to identify at nucleotide resolution the 3´ ends targeted by the nuclear exosome, and determine the sites of NNS-dependent termination genome-wide. Overall design: 3´-end mapping of wild-type and various nuclear exosome mutant strains, either using gene knockouts or the anchor away system to conditionally deplete FRB-tagged proteins from the nucleus
Common genomic elements promote transcriptional and DNA replication roadblocks.
Subject
View SamplesWe report the effects of Rapamycin treatment on the transcriptome of normal human dermal fibroblasts isolated from foreskin (designated 2DD). We sequenced mRNA from 2 replicates of proliferative (PRO) quiescent (QUI, serum starved) or treated with 500nM Rapamycin for 5 days (RAP). Comparative analyses with PRO transcripts a baseline indicate that genes that changed expression from Rapamycin treated fibroblasts are significantly different from those of quiescence cells. Rapamycin treated cells showed a significant enrichment for cytokines from the Il-6 cascade. Overall design: Examination of mRNAs from proliferative, quiescent (serum starvation) and Rapamycin (5oonM, 5days) treated 2DD normal human dermal/foreskin fibroblasts.
Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts.
No sample metadata fields
View SamplesInner ear auditory and vestibular tissues differ in their responses to mechanical stimuli.
Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity.
Specimen part
View SamplesThe incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups.
Tumor immunobiological differences in prostate cancer between African-American and European-American men.
Race
View SamplesAncestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individuals life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring the phenotype into being.
Epigenetic transgenerational inheritance of altered stress responses.
Sex, Specimen part
View SamplesCell transformation by the Src tyrosine kinase is characterized by extensive changes in gene expression. To describe these changes, investigators have relied extensively on the study of immortalized rodent cell lines or heterogeneous tumor samples that limit the identification of differentially expressed genes or may not represent the full spectrum of biological processes regulated during transformation. In this study, we took advantage of transformation-deficient and temperature sensitive mutants of the Rous sarcoma virus to characterize the patterns of gene expression in two types of primary cells, namely chicken embryo fibroblasts (CEF) and chicken neuro-retinal (CNR) cells.
Cellular processes of v-Src transformation revealed by gene profiling of primary cells--implications for human cancer.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease.
Sex, Age, Treatment, Race
View SamplesThe goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays.
DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease.
Sex, Age, Treatment, Race
View SamplesWith the aim of identifying new pathways and genes regulated by PTH(1-34) and PTH-related protein 1-141 [PTHrP(1-141)] in osteoblasts, this study was carried out using a mouse marrow stromal cell line, Kusa 4b10, that acquires features of the osteoblastic phenotype in long-term culture conditions. After the appearance of functional PTH receptor 1 (PTHR1) in Kusa 4b10 cells, they were treated with either PTH(1-34) or PTHrP(1-141), and RNA was subjected to Affymetrix whole mouse genome array.
EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts.
Specimen part, Cell line
View Samples