Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of long noncoding RNAs during pancreas development

ABSTRACT: LncRNAs are developmentally regulated and highly cell type-specific non-coding RNAs that have emerged as important regulators of cell fate commitment and maintenance. In this study, we dissected the role of lncRNAs in human pancreas development by classifying lncRNAs based on their dynamic regulation, subcellular localization, and engagement with ribosomes during the stepwise differentiation of human embryonic stem cells (hESCs) towards pancreatic fate. We then deleted 10 candidate lncRNAs in hESCs and characterized the knockout phenotypes of pancreatic developmental intermediates, prioritizing dynamically regulated lncRNAs with validated translation potential and proximity to developmental TFs. This small-scale loss-of-function screen revealed that most lncRNAs are dispensable for pancreatic development and the regulation of nearby genes. We identify LINC00261 as the first translated lncRNA involved in human endocrine cell development, and show that it regulates gene expression in pancreatic progenitor cells in trans rather than cis. Through systematic dissection of LINC00261's coding and noncoding functions, we can exclude a role for the produced micropeptides in this process. Instead, we posit that, over the course of pancreatic differentiation, the biological activity of multiple lncRNAs is controlled by a regulatory, translation machinery dependent mechanism that employs ribosome engagement and short open reading frame translation to dose lncRNA activity in the nucleus. It is conceivable that inadequate nuclear LINC00261 dosage during human pancreas development could predispose individuals to developing diabetes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144682 | GEO | 2020/08/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Viral infection identifies micropeptides differentially regulated in smORF-containing lncRNA

Project description:We use genome-wide high-throughput methods to identify potential micropeptides in smORF containing lncRNA involved in the immune response. Using influenza as a viral infection model, we performed RNAseq and ribosome profiling to track expression and translation of putative lncRNAs that encode for peptides and identify tens of potential candidates.

2017-07-31 | GSE101760 | GEO

Translation and Natural Selection of long non-canonical RNA micropeptides

Project description:Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but lacking canonical coding sequences. Apparently unable to produce peptides, lncRNA function seems to only involve RNA sequence and structure. Here, we exhaustively detect in-vivo translation of small open reading frames (small ORFs) within lncRNAs using Ribosomal profiling during Drosophila melanogaster embryogenesis. We show that around 30% of lncRNAs contain small ORFs engaged by ribosomes, leading to regulated translation of 100 to 300 micropeptides. We identify lncRNA features that favour translation, such as cistronicity, Kozak sequences, and conservation. For this latter, we develop a bioinformatics pipeline to detect small ORF homologues, and we reveal evidence of natural selection favouring the conservation of micropeptide sequence and function across evolution. Our results expand the repertoire of lncRNA functions, and suggest that lncRNAs give rise to novel coding genes throughout evolution. Since most lncRNAs contain small ORFs with as yet unknown translation potential, we propose to rename them “long non-canonical RNAs”.

2022-11-02 | GSE204739 | GEO

Elucidation of the role of murine lncRNA LL35 in hepatocytes by LC-MSMS

Project description:Long non-coding RNAs (lncRNAs) play important roles in the regulation of many biological processes in the cell like transcription, translation, splicing, transport, etc. More than 10K lncRNAs are predicted in human, but functions for the majority remain unknown. LncRNAs may contribute to the development of multiple diseases that makes them perspective diagnostic and prognostic markers as well as drug targets [1]. Murine lncRNA Falcor/LL35 is a proposed functional analog of human lncRNA DEANR1, which is predominantly expressed in murine lungs and liver, intestine and pancreas [2, 3]. While the participation of LL35 in LL35–Foxa2 (transcription factor) regulatory loop during regeneration after lung injury was previously described by Swarr et al. [2], its functional role in murine liver remains unknown. In our work we focused on revealing the role of murine lncRNA LL35 in hepatocytes and in mouse liver. We analyzed changes in proteome of AML12 (normal hepatocytes) cell line on the 2nd day after LL35 depletion. [1] Morlando, M., Ballarino, M., & Fatica, A. (2015). Long non-coding RNAs: New players in hematopoiesis and leukemia. Frontiers in Medicine, Vol. 2. [2] Swarr, D. T., Herriges, M., Li, S., Morley, M., Fernandes, S., Sridharan, A., … Morrisey, E. E. (2019). The long noncoding RNA Falcor regulates Foxa2 expression to maintain lung epithelial homeostasis and promote regeneration. Genes & Development, 33(11-12), 656–668. [3] Sergeeva, O. V, Korinfskaya, S. A., Kurochkin, I. I., & Zatsepin, T. S. (2019). Long Noncoding RNA LL35 / Falcor Regulates Expression of Transcription Factor Foxa2 in Hepatocytes in Normal and Fibrotic Mouse Liver. Acta Naturae, 11(42), 66–74.

2022-08-11 | PXD033910 | Pride

Screening for micropeptides in HUVEC without tryptic digestion, part 1

Project description:Long non-coding RNAs (lncRNA) are transcribed but not translated ribonucleic acids with various functions. We analyzed a so far unreported lncRNA n342419, which we named MANTIS. A search for micropeptides after overexpression of MANTIS in Human Umbilical Vein Endothelial Cells (HUVEC) with subsequent LC-MS/MS without trypsination showed that none of the micropeptides found had any similarity to potential MANTIS ORFs, whereas the positive control yielded micropeptides encoded from GFP plasmid.

2017-03-27 | PXD005951 | Pride

Pancreatic progenitor epigenome maps prioritize type 2 diabetes risk genes with roles in development

Project description:Genetic variants associated with type 2 diabetes (T2D) risk affect gene regulation in metabolically relevant tissues, such as pancreatic islets. Here, we investigated contributions of regulatory programs active during pancreatic development to T2D risk. Interrogation of chromatin maps from developmental precursors throughout pancreatic differentiation of human embryonic stem cells (hESCs) identifies enrichment of T2D variants in pancreatic progenitor-specific stretch enhancers that are not active in islets. Genes associated with progenitor-specific stretch enhancers are predicted to regulate developmental processes, most notably tissue morphogenesis. Through gene editing in hESCs, we demonstrate that progenitor-specific enhancers harboring T2D-associated variants regulate cell polarity genes LAMA1 and CRB2. Knockdown of lama1 or crb2 in zebrafish embryos causes a defect in pancreas morphogenesis and impairs islet cell development. Together, our findings reveal that a subset of T2D risk variants specifically affects pancreatic developmental programs, suggesting that dysregulation of developmental processes can predispose to T2D.

2021-01-19 | GSE149148 | GEO

TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation

Project description:Current knowledge about the role of epigenetic modifiers in pancreas development has been exponentially increased. However, the precise function of TET dioxygenases in pancreas specification remains poorly understood. Using a stepwise human embryonic stem cell (hESC) differentiation system, TET1/TET2/TET3 triple-knockout (TKO) cells displayed severe defects in pancreatic differentiation. Whole-genome analysis revealed TET depletion led to aberrant DNA methylation and chromatin remodeling. In comparison with methylome and hydroxymethylome datasets previously generated from hESCs, we identified unique pancreas-specific hyper-methylated and hypo-hydroxymethylated regions in TKO cells, where binding of pioneer transcription factor FOXA2 was remarkably enriched. Interestingly, transduction of full-length TET1 in TKO cells effectively rescued pancreatic differentiation and the expression of PAX4, a key determinant for -cell specification. Taking these findings together with genome-wide mapping of TET1 in pancreatic progenitors, we uncovered that TET1 co-occupied at a specific subset of FOXA2-bound loci featuring high levels of active chromatin. Locus-specific DNA methylation analysis revealed significant increases of 5-methylcytosine at the PAX4 enhancer in a TET1-dependent manner, consistent with defective generation of functional beta-cells from TET1-knockout hESCs. Thus, our study not only highlights the importance of TET-dependent epigenetic regulation in pancreas development but also unveils an essential role of TET1 in establishing beta-cell identity.

2022-04-13 | GSE146486 | GEO

Screening for micropeptides in HUVEC with tryptic digestion, part 2

Project description:Long non-coding RNAs (lncRNA) are transcribed but not translated ribonucleic acids with various functions. We analyzed a so far unreported lncRNAn 342419, which we named MANTIS. A search for micropeptides after overexpression of MANTIS in Human Umbilical Vein Endothelial Cells (HUVEC) with subsequent LC-MS/MS with trypsination showed that none of the micropeptides found had any similarity to potential MANTIS ORFs.

2017-03-27 | PXD005957 | Pride

Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo [RNA CaptureSeq]

Project description:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. RNA CaptureSeq was perfomed on RNA extracted from adult mouse subventricular zone to better characterize rare lncRNA isoforms. Genomic regions used to design capture array are included in the raw file target_regions.bed.

2013-04-11 | E-GEOD-45277 | biostudies-arrayexpress

Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo [ChIP-seq]

Project description:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. CHIP-seq was performed on SVZ-derived neurospheres to determine the chromatin state of lncRNA promoters in adult neural stem cells

2013-04-11 | E-GEOD-45279 | biostudies-arrayexpress

One-shot analysis of translated mammalian lncRNAs with AHARIBO

Project description:A vast portion of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs) acting in the cytoplasm with largely unknown functions. Surprisingly, lncRNAs have been shown to interact with ribosomes, encode uncharacterized proteins, or act as ribosome sponges. These functions still remain mostly undetected and understudied owing to the lack of efficient tools for genome-wide simultaneous identification of ribosome-associated lncRNAs and peptide-producing lncRNAs. Here we present AHARIBO, a method for the detection of lncRNAs either untranslated, but associated with ribosomes, or encoding small peptides. Using AHARIBO in mouse embryonic stem cells during neuronal differentiation, we isolated ribosome-protected RNA fragments, translated RNAs and corresponding de novo synthesized polypeptides. Besides identifying mRNAs under active translation and associated ribosomes, we found and distinguished lncRNAs acting as ribosome sponges or encoding micropeptides, laying the ground for a better functional understanding of hundreds lncRNAs.

2021-09-09 | PXD022679 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data