scholarly journals When Long Noncoding RNAs Meet Genome Editing in Pluripotent Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-13
Author(s):  
Fuquan Chen ◽  
Jiaojiao Ji ◽  
Jian Shen ◽  
Xinyi Lu
Keyword(s):  
Stem Cells ◽  
Transcriptional Regulation ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Biological Processes ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
The Past

Most of the human genome can be transcribed into RNAs, but only a minority of these regions produce protein-coding mRNAs whereas the remaining regions are transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) were known for their influential regulatory roles in multiple biological processes such as imprinting, dosage compensation, transcriptional regulation, and splicing. The physiological functions of protein-coding genes have been extensively characterized through genome editing in pluripotent stem cells (PSCs) in the past 30 years; however, the study of lncRNAs with genome editing technologies only came into attentions in recent years. Here, we summarize recent advancements in dissecting the roles of lncRNAs with genome editing technologies in PSCs and highlight potential genome editing tools useful for examining the functions of lncRNAs in PSCs.

scholarly journals Predicting the Functions of Long Noncoding RNAs Using RNA-Seq Based on Bayesian Network

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Yun Xiao ◽  
Yanling Lv ◽  
Hongying Zhao ◽  
Yonghui Gong ◽  
Jing Hu ◽  
...  
Keyword(s):  
Bayesian Network ◽  
Regulatory Network ◽  
Noncoding Rnas ◽  
Nervous System Development ◽  
Long Noncoding Rnas ◽  
Functional Enrichment ◽  
Biological Processes ◽  
Rna Seq ◽  
Protein Coding ◽  
Protein Coding Genes

Long noncoding RNAs (lncRNAs) have been shown to play key roles in various biological processes. However, functions of most lncRNAs are poorly characterized. Here, we represent a framework to predict functions of lncRNAs through construction of a regulatory network between lncRNAs and protein-coding genes. Using RNA-seq data, the transcript profiles of lncRNAs and protein-coding genes are constructed. Using the Bayesian network method, a regulatory network, which implies dependency relations between lncRNAs and protein-coding genes, was built. In combining protein interaction network, highly connected coding genes linked by a given lncRNA were subsequently used to predict functions of the lncRNA through functional enrichment. Application of our method to prostate RNA-seq data showed that 762 lncRNAs in the constructed regulatory network were assigned functions. We found that lncRNAs are involved in diverse biological processes, such as tissue development or embryo development (e.g., nervous system development and mesoderm development). By comparison with functions inferred using the neighboring gene-based method and functions determined using lncRNA knockdown experiments, our method can provide comparable predicted functions of lncRNAs. Overall, our method can be applied to emerging RNA-seq data, which will help researchers identify complex relations between lncRNAs and coding genes and reveal important functions of lncRNAs.

scholarly journals Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew N. George ◽  
Karla F. Leavens ◽  
Paul Gadue
Keyword(s):  
Stem Cells ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Genetic Disease ◽  
Single Gene ◽  
Monogenic Diabetes ◽  
Human Pluripotent Stem Cells ◽  
Genetic Modifiers ◽  
Β Cell ◽  
Protein Coding

A mechanistic understanding of the genetic basis of complex diseases such as diabetes mellitus remain elusive due in large part to the activity of genetic disease modifiers that impact the penetrance and/or presentation of disease phenotypes. In the face of such complexity, rare forms of diabetes that result from single-gene mutations (monogenic diabetes) can be used to model the contribution of individual genetic factors to pancreatic β-cell dysfunction and the breakdown of glucose homeostasis. Here we review the contribution of protein coding and non-protein coding genetic disease modifiers to the pathogenesis of diabetes subtypes, as well as how recent technological advances in the generation, differentiation, and genome editing of human pluripotent stem cells (hPSC) enable the development of cell-based disease models. Finally, we describe a disease modifier discovery platform that utilizes these technologies to identify novel genetic modifiers using induced pluripotent stem cells (iPSC) derived from patients with monogenic diabetes caused by heterozygous mutations.

scholarly journals Epigenetic Regulation of Dental Pulp Stem Cell Fate

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Dan Zhou ◽  
Lu Gan ◽  
Yiran Peng ◽  
Yachuan Zhou ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
Dental Pulp ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Stem Cell Fate ◽  
The Past ◽  
Multipotent Differentiation ◽  
Dental Pulp Stem Cell

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

Identify the critical protein‐coding genes and long noncoding RNAs in cardiac myxoma

2019 ◽  
Vol 120 (8) ◽  
pp. 13441-13452 ◽  
Author(s):  
Nan Cheng ◽  
Yuanbin Wu ◽  
Huajun Zhang ◽  
Yi Guo ◽  
Huimin Cui ◽  
...  
Keyword(s):  
Cardiac Myxoma ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Protein Coding Genes

scholarly journals Short-lived long noncoding RNAs as surrogate indicators for chemical stress in HepG2 cells and their degradation by nuclear RNases

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hidenori Tani ◽  
Ayaka Numajiri ◽  
Motohide Aoki ◽  
Tomonari Umemura ◽  
Tetsuya Nakazato
Keyword(s):  
Stress Responses ◽  
Hepg2 Cells ◽  
Noncoding Rnas ◽  
Heavy Metal Stress ◽  
Chemical Exposure ◽  
Long Noncoding Rnas ◽  
Chemical Stress ◽  
Biological Processes ◽  
Protein Coding ◽  
Regulatory Functions

AbstractLong noncoding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length that have been shown to play important roles in various biological processes. The mechanisms underlying the induction of lncRNA expression by chemical exposure remain to be determined. We identified a novel class of short-lived lncRNAs with half-lives (t1/2) ≤4 hours in human HeLa Tet-off cells, which have been suggested to express many lncRNAs with regulatory functions. As they may affect various human biological processes, short-lived lncRNAs may be useful indicators of the degree of stress on chemical exposure. In the present study, we identified four short-lived lncRNAs, designated as OIP5-AS1, FLJ46906, LINC01137, and GABPB1-AS1, which showed significantly upregulated expression following exposure to hydrogen peroxide (oxidative stress), mercury II chloride (heavy metal stress), and etoposide (DNA damage stress) in human HepG2 cells. These lncRNAs may be useful indicators of chemical stress responses. The levels of these lncRNAs in the cells were increased because of chemical stress-induced prolongation of their decay. These lncRNAs were degraded by nuclear RNases, which are components of the exosome and XRN2, and chemical exposure inhibited the RNase activities within the cells.

scholarly journals Full-length annotation with multi-strategy RNA-seq uncovers transcriptional regulation of lncRNAs in diploid cotton G. arboreum1

2020 ◽  
Author(s):  
Xiaomin Zheng ◽  
Yanjun Chen ◽  
Yifan Zhou ◽  
Danyang Li ◽  
Keke Shi ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Full Length ◽  
Rna Seq ◽  
Accurate Identification ◽  
Tissue Samples ◽  
Protein Coding ◽  
Diploid Cotton ◽  
Cap Analysis

AbstractLong noncoding RNAs (lncRNAs) are crucial factors during plant development and environmental responses. High-throughput and accurate identification of lncRNAs is still lacking in plants. To build an accurate atlas of lncRNA in cotton, we combined Isoform-sequencing (Iso-seq), strand-specific RNA-seq (ssRNA-seq), cap analysis gene expression (CAGE-seq) with PolyA-seq and compiled a pipeline named plant full-length lncRNA (PULL) to integrate multi-omics data. A total of 9240 lncRNAs from 21 tissue samples of the diploid cotton Gossypium arboreum were identified. We revealed that alternative usage of transcription start site (TSS) and transcription end site (TES) of lncRNAs occurs pervasively during plant growth and responses to stress. We identified the lncRNAs which co-expressed or be linked to the protein coding genes (PCGs) or GWAS studied SNPs associated with ovule and fiber development. We also mapped the genome-wide binding sites of two lncRNAs with chromatin isolation by RNA purification sequencing (ChIRP-seq) and validated the trans transcriptional regulation of lnc-Ga13g0352 via virus induced gene suppression (VIGS) assay. These findings provide valuable research resources for plant community and broaden our understandings of biogenesis and regulation function of plant lncRNAs.One sentence summaryThe full-length annotation and transcriptional regulation of long noncoding RNAs in cotton.

scholarly journals RNA sequencing analysis of altered expression of long noncoding RNAs associated with Schistosoma japonicum infection in the murine liver and spleen

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Tianqi Xia ◽  
Bikash Ranjan Giri ◽  
Jingyi Liu ◽  
Pengfei Du ◽  
Xue Li ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Schistosoma Japonicum ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Protein Coding ◽  
Altered Expression ◽  
Protein Coding Genes

Abstract Background Schistosomiasis is a chronic, debilitating infectious disease caused by members of the genus Schistosoma. Previous findings have suggested a relationship between infection with Schistosoma spp. and alterations in the liver and spleen of infected animals. Recent reports have shown the regulatory role of noncoding RNAs, such as long noncoding RNAs (lncRNAs), in different biological processes. However, little is known about the role of lncRNAs in the mouse liver and spleen during Schistosoma japonicum infection. Methods In this study, we identified and investigated lncRNAs using standard RNA sequencing (RNA-Seq). The biological functions of the altered expression of lncRNAs and their target genes were predicted using bioinformatics. Ten dysregulated lncRNAs were selected randomly and validated in reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) experiments. Results Our study identified 29,845 and 33,788 lncRNAs from the liver and spleen, respectively, of which 212 were novel lncRNAs. We observed that 759 and 789 of the lncRNAs were differentially expressed in the respective organs. The RT-qPCR results correlated well with the sequencing data. In the liver, 657 differentially expressed lncRNAs were predicted to target 2548 protein-coding genes, whereas in the spleen 660 differentially expressed lncRNAs were predicted to target 2673 protein-coding genes. Moreover, functional annotation showed that the target genes of the differentially expressed lncRNAs were associated with cellular processes, metabolic processes, and binding, and were significantly enriched in metabolic pathways, the cell cycle, ubiquitin-mediated proteolysis, and pathways in cancer. Conclusions Our study showed that numerous lncRNAs were differentially expressed in S. japonicum-infected liver and spleen compared to control liver and spleen; this suggested that lncRNAs may be involved in pathogenesis in the liver and spleen during S. japonicum infection.

scholarly journals Dysregulated Expression of Long Noncoding RNAs in Ovarian Cancer

2016 ◽  
Vol 26 (9) ◽  
pp. 1564-1570 ◽  
Author(s):  
Yancheng Zhong ◽  
Dan Gao ◽  
Shiwei He ◽  
Cijun Shuai ◽  
Shuping Peng
Keyword(s):  
Ovarian Cancer ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Biological Processes ◽  
Gynecologic Malignancies ◽  
Protein Coding ◽  
Step Process ◽  
Biomarker Molecules ◽  
Novel Therapeutic ◽  
Multiple Step

AbstractOvarian cancer is the leading cause of death among women with gynecologic malignancies. The development and progression of ovarian cancer are complex and a multiple-step process. New biomarker molecules for diagnostic and prognostic are essential for novel therapeutic targets and to extend the survival time of patients with ovarian cancer. Long noncoding RNAs (lncRNAs) are non–protein-coding transcripts longer than 200 nucleotides that have recently been found as key regulators of various biological processes and to be involved in the development and progression of many diseases including cancers. In this review, we summarized the expression pattern of several dysregulated lncRNAs (HOTAIR, H19, XIST, and HOST2) and the functional molecular mechanism of these lncRNAs on the initiation and progression of ovarian cancer. The lncRNAs as biomarkers may be used for current and future clinical diagnosis, therapeutics, and prognosis.

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