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Repeat elements study in pluripotent stem cells [expression array]

ABSTRACT: We surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54725 | GEO | 2014/10/09

SECONDARY ACCESSION(S): PRJNA237585

REPOSITORIES: GEO

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repeat elements study in pluripotent stem cells [expression array]

Project description:We surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis. Total of 18 samples of the human ESC line H9 were analyzed for gene expression.

2014-10-09 | E-GEOD-54725 | biostudies-arrayexpress

Repeat elements study in pluripotent stem cells [RNA-seq]

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Repeat elements study in pluripotent stem cells [RNA-seq]

Project description:We surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. Poly(A)+ RNA extraction and further sequencing library construction was done for two types of cells (iPS, HFF-1) and hiPSC-derived embryoid bodies following Illumina TruSeq RNA Sample Preparation Kit protocol, which was further sequenced on Illumina HiSeq machine with single-end 101 cycles.

2014-10-09 | E-GEOD-44646 | biostudies-arrayexpress

siRNA profiling of human colon cancer HT29 cells, siHX transfected vs. control

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Co-IP of fHERV-K env protein and interactors

Project description:This project seeks to identify protein-protein interactions with human endogenous retrovirus K envelope protein. A flag-tagged HERV-K env construct (fHERV-K env) was expressed in HEK293 cells. An anti-flag MAb was immobilized on magnetic protein G beads was used to capture fHERV-K env and interactors.

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Transposable elements and small RNAs contribute to gene expression divergence between Arabidopsis thaliana and Arabidopsis lyrata [RNA-Seq]

Project description:Transposable elements (TEs) are often the primary determinant of genome size differences among eukaryotes. In plants, the proliferation of TEs is countered through epigenetic silencing mechanisms that prevent transposition. Recent studies using the model plant Arabidopsis thaliana have revealed that methylated TE insertions are often associated with reduced expression of nearby genes, and these insertions may be subject to purifying selection due to their effect on nearby genes. Less is known about the genome-wide patterns of epigenetic silencing of TEs in other plant species. Here, we compare the 24-nt siRNA complement from Arabidopsis thaliana and a closely related congener with a two- to three-fold higher TE copy number, A. lyrata. We show that TEs, and particularly siRNA-targeted TEs, are associated with reduced gene expression within both species and also with gene expression differences between orthologs. In addition, A. lyrata TEs are targeted by a lower fraction of uniquely matching siRNAs, which are associated with more effective silencing of TE expression. Overall, our results suggest that the efficacy of RNA-directed DNA methylation silencing is lower in A. lyrata, a finding that may shed light on the causes of differential TE proliferation among species. 4 A. lyrata mRNA-seq samples

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Human Neutrophils in Pulmonary Arterial Hypertension by LC-MSMS

Project description:Neutrophil elastase (NE) is implicated in pulmonary arterial hypertension (PAH) but the role of neutrophils in the pathogenesis of PAH is unclear. Here we show that neutrophils from PAH vs. control subjects produce and release increased NE associated with enhanced extracellular trap formation. PAH neutrophils are highly adherent and show decreased migration consistent with increased vinculin, identified on proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic interferon signature in PAH neutrophils and an increase in human endogenous retrovirus (HERV-K) envelope protein. NE and interferon genes are induced by HERV-K envelope and vinculin is increased by HERV-K dUTPase that is elevated in PAH plasma. Neutrophil exosomes from PAH plasma contain increased NE and HERV-K envelope and induce pulmonary hypertension in mice, that is mitigated by the NE inhibitor and antiviral agent, elafin. Thus elevated HERVs explain pathological neutrophils linked to PAH induction and progression.

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A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins

Project description:The human genome consists of considerable portions derived from retroviruses typically inherited already for millions of years. So-called human endogenous retroviruses (HERVs) are usually severely mutated, yet some coding-competent HERV sequences exist. The HERV-K(HML-2) group includes evolutionarily young proviruses that still encode typical retroviral proteins. HERV-K(HML-2) has been implicated in various human diseases because transcription is often upregulated and encoded proteins are known to affect cell biology. HERV-K(HML-2) protease has received little attention so far. With findings for Human Immunodeficiency Virus (HIV) protease in mind we set out to identify human cellular proteins being substrates of HERV-K(HML-2) protease employing a modified Terminal Amine Isotopic Labeling of Substrates (TAILS) procedure. Thousands of significantly processed human proteins were revealed by TAILS and we could verify cleavage of a majority of selected human proteins in vitro. Our analysis suggests that hundreds, if not thousands of cellular proteins are potential substrates of HERV-K(HML-2) protease. As identified proteins participate in diverse, often disease-relevant cellular processes, it is conceivable that expression of HERV-K(HML-2) protease has functional consequences for cell biology and thus development of human diseases. Endogenous retrovirus-encoded protease may also be relevant for disease development in species other than human.

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Human Endogenous Retrovirus-K in Stem Cell Function and Neuronal Differentiation [dataset 2]

Project description:Human endogenous retrovirus (HERV) genes were incorporated into the genome over millions of years but they mostly have inactivating mutations. HERV-K is the most recently incorporated virus. Incidental HERV-K gene expression occurs in a variety of pathological conditions. However, its physiological role is poorly understood. To study the role of HERV-K in development, we monitored its expression and function in pluripotent stem cells and during the process of neuronal differentiation. The expression of HERV-K env was localized to chromosomes 12 and 19. HERV-K Env was expressed on the cell surface of pluripotent stem cells and was critical in maintaining the stemness and adhesion of the cells. Interactions with CD98HC resulted in activation of signaling pathways that regulate stem cells genes. Down regulation of HERV-K env resulted in dissociation of the stem cell colonies and enhanced differentiation along neuronal pathways. HERV-K env expression during neurodevelopment was regulated by DNA methylation. Thus, HERV-K regulation is critical for human embryonic and neurodevelopment.

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