scholarly journals Characterization of novel primary miRNA transcription units in human cells using Bru-seq nascent RNA sequencing

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Karan Bedi ◽  
Michelle T Paulsen ◽  
Thomas E Wilson ◽  
Mats Ljungman
Keyword(s):  
Rna Polymerase Ii ◽  
Rna Sequencing ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Mature Mirnas ◽  
Mirna Regulation ◽  
Cell Type ◽  
Data Resource ◽  
Cell Type Specific ◽  
Nascent Rna

Abstract MicroRNAs (miRNAs) are key contributors to gene regulatory networks. Because miRNAs are processed from RNA polymerase II transcripts, insight into miRNA regulation requires a comprehensive understanding of the regulation of primary miRNA transcripts. We used Bru-seq nascent RNA sequencing and hidden Markov model segmentation to map primary miRNA transcription units (TUs) across 32 human cell lines, allowing us to describe TUs encompassing 1443 miRNAs from miRBase and 438 from MirGeneDB. We identified TUs for 61 miRNAs with an unknown CAGE TSS signal for MirGeneDB miRNAs. Many primary transcripts containing miRNA sequences failed to generate mature miRNAs, suggesting that miRNA biosynthesis is under both transcriptional and post-transcriptional control. In addition to constitutive and cell-type specific TU expression regulated by differential promoter usage, miRNA synthesis can be regulated by transcription past polyadenylation sites (transcriptional read through) and promoter divergent transcription (PROMPTs). We identified 197 miRNA TUs with novel promoters, 97 with transcriptional read-throughs and 3 miRNA TUs that resemble PROMPTs in at least one cell line. The miRNA TU annotation data resource described here reveals a greater complexity in miRNA regulation than previously known and provides a framework for identifying cell-type specific differences in miRNA transcription in cancer and cell transition states.

scholarly journals Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types

2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  
Keyword(s):  
Blood Cell ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Spatial Organization ◽  
Cell Types ◽  
Gene Promoters ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Insight Into

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.

scholarly journals Cell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christopher A. Brosnan ◽  
Alexander J. Palmer ◽  
Steven Zuryn
Keyword(s):  
Caenorhabditis Elegans ◽  
Regulatory Networks ◽  
Regulatory Mechanisms ◽  
Cell Type ◽  
A Genome ◽  
Temporal Flexibility ◽  
Small Regulatory Rnas ◽  
Cell Type Specific ◽  
Single Cell Type ◽  
Regulated Gene Expression

AbstractMulticellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.

scholarly journals Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205883 ◽  
Author(s):  
Joseph C. Mays ◽  
Michael C. Kelly ◽  
Steven L. Coon ◽  
Lynne Holtzclaw ◽  
Martin F. Rath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pineal Gland ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific ◽  
Mammalian Pineal Gland ◽  
Daily Patterns

scholarly journals Single-cell RNA sequencing reveals cell type- and artery type-specific vascular remodelling in male spontaneously hypertensive rats

2020 ◽  
Author(s):  
Jun Cheng ◽  
Wenduo Gu ◽  
Ting Lan ◽  
Jiacheng Deng ◽  
Zhichao Ni ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Spontaneously Hypertensive Rats ◽  
Cell Types ◽  
Vascular Remodelling ◽  
Cell Type ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific

Abstract Aims Hypertension is a major risk factor for cardiovascular diseases. However, vascular remodelling, a hallmark of hypertension, has not been systematically characterized yet. We described systematic vascular remodelling, especially the artery type- and cell type-specific changes, in hypertension using spontaneously hypertensive rats (SHRs). Methods and results Single-cell RNA sequencing was used to depict the cell atlas of mesenteric artery (MA) and aortic artery (AA) from SHRs. More than 20 000 cells were included in the analysis. The number of immune cells more than doubled in aortic aorta in SHRs compared to Wistar Kyoto controls, whereas an expansion of MA mesenchymal stromal cells (MSCs) was observed in SHRs. Comparison of corresponding artery types and cell types identified in integrated datasets unravels dysregulated genes specific for artery types and cell types. Intersection of dysregulated genes with curated gene sets including cytokines, growth factors, extracellular matrix (ECM), receptors, etc. revealed vascular remodelling events involving cell–cell interaction and ECM re-organization. Particularly, AA remodelling encompasses upregulated cytokine genes in smooth muscle cells, endothelial cells, and especially MSCs, whereas in MA, change of genes involving the contractile machinery and downregulation of ECM-related genes were more prominent. Macrophages and T cells within the aorta demonstrated significant dysregulation of cellular interaction with vascular cells. Conclusion Our findings provide the first cell landscape of resistant and conductive arteries in hypertensive animal models. Moreover, it also offers a systematic characterization of the dysregulated gene profiles with unbiased, artery type-specific and cell type-specific manners during hypertensive vascular remodelling.

scholarly journals Post-transcriptional control of cellular differentiation by the RNA exosome complex

2020 ◽  
Vol 48 (21) ◽  
pp. 11913-11928
Author(s):  
Isabela Fraga de Andrade ◽  
Charu Mehta ◽  
Emery H Bresnick
Keyword(s):  
Cellular Differentiation ◽  
Transcriptional Control ◽  
Cell Type ◽  
Protein Coding ◽  
Regulatory Machinery ◽  
Regulatory Complex ◽  
Cell Type Specific ◽  
Rna Exosome ◽  
Post Transcriptional Regulation ◽  
Exosome Complex

Abstract Given the complexity of intracellular RNA ensembles and vast phenotypic remodeling intrinsic to cellular differentiation, it is instructive to consider the role of RNA regulatory machinery in controlling differentiation. Dynamic post-transcriptional regulation of protein-coding and non-coding transcripts is vital for establishing and maintaining proteomes that enable or oppose differentiation. By contrast to extensively studied transcriptional mechanisms governing differentiation, many questions remain unanswered regarding the involvement of post-transcriptional mechanisms. Through its catalytic activity to selectively process or degrade RNAs, the RNA exosome complex dictates the levels of RNAs comprising multiple RNA classes, thereby regulating chromatin structure, gene expression and differentiation. Although the RNA exosome would be expected to control diverse biological processes, studies to elucidate its biological functions and how it integrates into, or functions in parallel with, cell type-specific transcriptional mechanisms are in their infancy. Mechanistic analyses have demonstrated that the RNA exosome confers expression of a differentiation regulatory receptor tyrosine kinase, downregulates the telomerase RNA component TERC, confers genomic stability and promotes DNA repair, which have considerable physiological and pathological implications. In this review, we address how a broadly operational RNA regulatory complex interfaces with cell type-specific machinery to control cellular differentiation.

scholarly journals Diverse nephron cell type‐specific adaptation to furosemide by morphometry and single cell RNA sequencing

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Steven Schaffert ◽  
Aram Krauson ◽  
Elisabeth Walczak ◽  
Jonathan Nizar ◽  
Gwendolyn Holdgate ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Cell Type ◽  
Specific Adaptation ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific

scholarly journals Dynamic regulatory module networks for inference of cell type specific transcriptional networks

2020 ◽  
Author(s):  
Alireza Fotuhi Siahpirani ◽  
Deborah Chasman ◽  
Morten Seirup ◽  
Sara Knaack ◽  
Rupa Sridharan ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Regulatory Networks ◽  
Network Dynamics ◽  
Cell Types ◽  
Small Sample ◽  
Cell Type ◽  
Regulatory Module ◽  
A Cell ◽  
Cell Type Specific ◽  
Time Point

AbstractChanges in transcriptional regulatory networks can significantly alter cell fate. To gain insight into transcriptional dynamics, several studies have profiled transcriptomes and epigenomes at different stages of a developmental process. However, integrating these data across multiple cell types to infer cell type specific regulatory networks is a major challenge because of the small sample size for each time point. We present a novel approach, Dynamic Regulatory Module Networks (DRMNs), to model regulatory network dynamics on a cell lineage. DRMNs represent a cell type specific network by a set of expression modules and associated regulatory programs, and probabilistically model the transitions between cell types. DRMNs learn a cell type’s regulatory network from input expression and epigenomic profiles using multi-task learning to exploit cell type relatedness. We applied DRMNs to study regulatory network dynamics in two different developmental dynamic processes including cellular reprogramming and liver dedifferentiation. For both systems, DRMN predicted relevant regulators driving the major patterns of expression in each time point as well as regulators for transitioning gene sets that change their expression over time.

scholarly journals Predicting gene regulatory networks from cell atlases

2020 ◽  
Author(s):  
Andreas Fønss Møller ◽  
Kedar Nath Natarajan
Keyword(s):  
Single Cell ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
Mouse Cell ◽  
Cell Type ◽  
Integrated Network ◽  
Mouse Tissues ◽  
Cell Type Specific ◽  
Gene Regulatory

AbstractRecent single-cell RNA-sequencing atlases have surveyed and identified major cell-types across different mouse tissues. Here, we computationally reconstruct gene regulatory networks from 3 major mouse cell atlases to capture functional regulators critical for cell identity, while accounting for a variety of technical differences including sampled tissues, sequencing depth and author assigned cell-type labels. Extracting the regulatory crosstalk from mouse atlases, we identify and distinguish global regulons active in multiple cell-types from specialised cell-type specific regulons. We demonstrate that regulon activities accurately distinguish individual cell types, despite differences between individual atlases. We generate an integrated network that further uncovers regulon modules with coordinated activities critical for cell-types, and validate modules using available experimental data. Inferring regulatory networks during myeloid differentiation from wildtype and Irf8 KO cells, we uncover functional contribution of Irf8 regulon activity and composition towards monocyte lineage. Our analysis provides an avenue to further extract and integrate the regulatory crosstalk from single-cell expression data.SummaryIntegrated single-cell gene regulatory network from three mouse cell atlases captures global and cell-type specific regulatory modules and crosstalk, important for cellular identity.

scholarly journals Cell Type-Specific Differentiation Between Indica and Japonica Rice Root Tip Responses to Different Environments Based on Single-Cell RNA Sequencing

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhe Wang ◽  
Daofu Cheng ◽  
Chengang Fan ◽  
Cong Zhang ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Rice Root ◽  
Differentially Expressed ◽  
Bzip Transcription Factor ◽  
Quiescent Center ◽  
Cell Type ◽  
Rice Varieties ◽  
Specific Differentiation ◽  
Cell Type Specific

Background: As Oryza sativa ssp. indica and Oryza sativa ssp. japonica are the two major subspecies of Asian cultivated rice, the adaptative evolution of these varieties in divergent environments is an important topic in both theoretical and practical studies. However, the cell type-specific differentiation between indica and japonica rice varieties in response to divergent habitat environments, which facilitates an understanding of the genetic basis underlying differentiation and environmental adaptation between rice subspecies at the cellular level, is little known.Methods: We analyzed a published single-cell RNA sequencing dataset to explore the differentially expressed genes between indica and japonica rice varieties in each cell type. To estimate the relationship between cell type-specific differentiation and environmental adaptation, we focused on genes in the WRKY, NAC, and BZIP transcription factor families, which are closely related to abiotic stress responses. In addition, we integrated five bulk RNA sequencing datasets obtained under conditions of abiotic stress, including cold, drought and salinity, in this study. Furthermore, we analyzed quiescent center cells in rice root tips based on orthologous markers in Arabidopsis.Results: We found differentially expressed genes between indica and japonica rice varieties with cell type-specific patterns, which were enriched in the pathways related to root development and stress reposes. Some of these genes were members of the WRKY, NAC, and BZIP transcription factor families and were differentially expressed under cold, drought or salinity stress. In addition, LOC_Os01g16810, LOC_Os01g18670, LOC_Os04g52960, and LOC_Os08g09350 may be potential markers of quiescent center cells in rice root tips.Conclusion: These results identified cell type-specific differentially expressed genes between indica-japonica rice varieties that were related to various environmental stresses and provided putative markers of quiescent center cells. This study provides new clues for understanding the development and physiology of plants during the process of adaptative divergence, in addition to identifying potential target genes for the improvement of stress tolerance in rice breeding applications.

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