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Multiple waves of transcriptome changes during extended hypoxic induction in human pulmonary microvascular endothelial cells

ABSTRACT: We profile the expression pattern of human pulmonary microvascular endothelial cells (HPMECs) at different time points of hypoxic stress. Through mRNA-seq, we identify functional waves of minor gene up-regulation at 8 and 24h hypoxia exposure followed by a massive wave of transcriptional activation after 48 hours. By weighted gene co-expression network analysis, we identify hub genes that likely play central roles in hypoxia transcription program. Strikingly, these hub genes included a prominent group of lincRNAs, suggesting non-coding RNAs may also have pivotal roles in the hypoxia regulatory circuit. HPMECs share a core hypoxia signature profile, but with some notably differences, indicating a portion of HPMECs hypoxia response is cell-specific. Collectively, our study comprehensive surveys the hypoxia transcriptome, and provides insight into the temporal dynamics of hypoxia transcriptional response. Time-course expression profiling of HPMECs exposed to hypoxia

ORGANISM(S): Homo sapiens

SUBMITTER: Kevin Huang

PROVIDER: E-GEOD-53510 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Multiple waves of transcriptome changes during extended hypoxic induction in human pulmonary microvascular endothelial cells

Project description:We profile the expression pattern of human pulmonary microvascular endothelial cells (HPMECs) at different time points of hypoxic stress. Through mRNA-seq, we identify functional waves of minor gene up-regulation at 8 and 24h hypoxia exposure followed by a massive wave of transcriptional activation after 48 hours. By weighted gene co-expression network analysis, we identify hub genes that likely play central roles in hypoxia transcription program. Strikingly, these hub genes included a prominent group of lincRNAs, suggesting non-coding RNAs may also have pivotal roles in the hypoxia regulatory circuit. HPMECs share a core hypoxia signature profile, but with some notably differences, indicating a portion of HPMECs hypoxia response is cell-specific. Collectively, our study comprehensive surveys the hypoxia transcriptome, and provides insight into the temporal dynamics of hypoxia transcriptional response.

2015-12-31 | GSE53510 | GEO

Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants [lncRNA-seq]

Project description:Background: LincRNAs play critical roles in eukaryotic cells, but systematic analyses of lincRNAs of an animal for phenotypes have been missing. We have generated CRISPR knockout strains for C. elegans lincRNAs and have evaluated their phenotypes Results: C. elegans lincRNAs demonstrate global features such as shorter length and fewer exons than mRNAs. For the systematic evaluation of C. elegans lincRNAs, CRISPR knockout strains for 155 out of all the 170 C. elegans lincRNAs were produced. Mutants of 23 lincRNAs have shown phenotypes in 6 traits analyzed. We have investigated these phenotypic lincRNAs for their gene expression patterns and their potential functional mechanisms. Some C. elegans lincRNAs play cis roles to modulate the expression of their neighboring genes, and some other lincRNAs play trans roles as ceRNAs against microRNAs. LincRNAs are extensively regulated by transcription factors, and we dissect the pathway that two transcription factors UNC-30 and UNC-55 control the expression of linc-73 together. Furthermore, linc-73 plays a cis role to modulate the expression of its neighboring gene unc-104, and thus regulates the formation of presynapses. Conclusions: By using CRISPR/cas9 technology, we have generated knockout strains of 155 C. elegans lincRNAs as valuable resources for studies in noncoding RNAs, and we provide biological insights for 23 phenotypic lincRNAs identified from 6 traits examined.

2018-12-27 | GSE115320 | GEO

Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants [ChIP-Seq]

2018-12-27 | GSE122973 | GEO

Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants [miRNA-seq]

2018-12-27 | GSE115321 | GEO

Transposable elements (TEs) contribute to stress-related long intergenic noncoding RNAs in Plants (I)

Project description:Long intergenic noncoding RNAs (lincRNAs) are widespread in cellular organisms, however, the origins and functions of many lincRNAs remain to be explored. Transposable elements (TEs) are widely distributed in many eukaryotic genomes, and often account for large fractions of plant and animal genomes. By using strand-specific RNA sequencing, we profiled the expression patterns of lincRNAs in Arabidopsis, rice and maize, and identified TE-associated lincRNAs (TE-lincRNAs). Stress regulation of some TE-lincRNAs was observed in Arabidopsis. Our findings indicate that TE-associated lincRNAs potentially play important roles in plant abiotic stress responses. Moreover, in the Arabidopsis chromatin remodelling mutant ddm1 that has an altered chromatin state, novel lincRNAs including TE-lincRNAs were generated. The novel lincRNAs were inherited in the subsequent generations in the wild type background, suggesting that lincRNAs could act as an adaptive reservoir in eukaryotes.

2017-01-21 | GSE76798 | GEO

Transposable elements (TEs) contribute to stress-related long intergenic noncoding RNAs in Plants (II)

2017-01-21 | GSE92419 | GEO

lincRNAs act in the circuitry controlling pluripotency and differentiation

Project description:While thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem cells (ESC) and characterized the effects on gene expression. Here we show that knockdown of lincRNAs have major consequences on gene expression patterns, comparable to knockdown of well-known ESC regulators. Notably, lincRNAs primarily affect gene expression in trans. We identify dozens of lincRNAs whose knockdown causes an exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ESCs and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts physically bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ESC state. We generated five lentiviral-based shRNAs targeting each of the 237 lincRNAs previously identified in ESCs. These shRNAs successfully targeted 147 lincRNAs and reduced their expression by an average of ~75% compared to endogenous levels in ESCs. As positive controls, we generated shRNAs targeting ~50 genes encoding regulatory proteins, including both transcription factor and chromatin factor genes that have been shown to play critical roles in ESC regulation; we obtained validated hairpins against 40 of these genes. As negative controls, we performed independent infections with lentiviruses containing 27 different shRNAs with no known cellular target RNA.

2011-08-29 | E-GEOD-30245 | biostudies-arrayexpress

Long Intergenic Noncoding RNAs regulated by SERRATE, CBP20 and CBP80

Project description:Long intergenic noncoding RNAs (lincRNAs) transcribed from intergenic regions play important roles in key biological processes.Analysis of published transcriptom datasets suggested some lincRNAs may be regulated by SERRATE,CBP20 and CBP80 in Arabidopsis. To further investigate the regulation, we use Arabidopsis lincRNA arrays v1 to detect lincRNA expression in se-2 and cbp20/80 double mutants.We found the expression levels of 940 lincRNAs (20%) out of the 4,634 lincRNAs with probes in array were significantly alerted in all mutants (P-value of eBays ANOVA < 0.05 & fold change of signal intensity > 2). This group included 525 up-regulated and 415 down-regulated lincRNAs. Seedlings(Col-0), Seedlings(se-2), Seedlings(cbp20,80 double mutant) x 3 biological replicates

2012-09-29 | E-GEOD-35963 | biostudies-arrayexpress

Long Intergenic Noncoding RNAs regulated by SERRATE, CBP20 and CBP80

2012-09-29 | GSE35963 | GEO

Conserved Function of lincRNAs in Vertebrate Embryonic Development Despite Rapid Sequence Evolution

Project description:Thousands of large intervening non-coding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data, to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation. H3K4me3, H3K36me3 chromatin maps, 3P-Seq and RNA-Seq were used to identify lincRNAs in the zebrafish genome

2011-12-22 | E-GEOD-32880 | biostudies-arrayexpress

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