Single-Cell RNA Sequencing of Retina:New Looks for Gene Marker and Old Diseases

Ying, Peixi; Chang, H. W.; Wang, Yan; Guo, Xiaojun; Cao, Yuchen; Zhang, Yuxi; Sheng, Fu; Chen, Lin; Yi, Guoguo; Fu, Min

doi:10.3389/fmolb.2021.699906

Cited by 9 publications

(8 citation statements)

References 63 publications

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“…Moreover, single-cell RNA sequencing (scRNA-seq)-based strategies can further increase the resolution of AS events to single retinal cell types. Such approaches have already been applied to the human retina in physiological and pathological conditions [ 42 – 45 ]. Combining the above-mentioned approaches can further delineate the complexity of the human retinal transcriptome.…”

Section: Discussionmentioning

confidence: 99%

Definition of the transcriptional units of inherited retinal disease genes by meta-analysis of human retinal transcriptome data

et al. 2023

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Background Inherited retinal diseases (IRD) are genetically heterogeneous disorders that cause the dysfunction or loss of photoreceptor cells and ultimately lead to blindness. To date, next-generation sequencing procedures fail to detect pathogenic sequence variants in coding regions of known IRD disease genes in about 30–40% of patients. One of the possible explanations for this missing heritability is the presence of yet unidentified transcripts of known IRD genes. Here, we aimed to define the transcript composition of IRD genes in the human retina by a meta-analysis of publicly available RNA-seq datasets using an ad-hoc designed pipeline. Results We analysed 218 IRD genes and identified 5,054 transcripts, 3,367 of which were not previously reported. We assessed their putative expression levels and focused our attention on 435 transcripts predicted to account for at least 5% of the expression of the corresponding gene. We looked at the possible impact of the newly identified transcripts at the protein level and experimentally validated a subset of them. Conclusions This study provides an unprecedented, detailed overview of the complexity of the human retinal transcriptome that can be instrumental in contributing to the resolution of some cases of missing heritability in IRD patients.

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Section: Discussionmentioning

confidence: 99%

Definition of the transcriptional units of inherited retinal disease genes by meta-analysis of human retinal transcriptome data

et al. 2023

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“…Genome-wide single-cell analysis represents the ultimate frontier of genomics research ( Boldt et al, 2016 ). In particular, scRNA-seq studies have been boosted in the last few years of new technologies enabling the study of the transcriptomic landscape of thousands of single cells in complex pathogenesis of diseases ( Ying et al, 2021 ). Owing to the dramatic improvement in scRNA-seq technology, especially integrating WGS and scRNA-seq, tissue-specific expression at the single-cell level has improved our understanding of biological processes ( Zeggini et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Liu

et al. 2021

Front. Genet.

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Background and Aims: The multiple renal cysts (MRC) occur in some patients with noncirrhotic portal hypertension (NCPH) could be a subset of ciliopathy. However, the potential genetic influencers and/or determinants in NCPH with MRC are largely unknown. The aim of this study was to explore the potential candidate variants/genes associated with those patients.Methods: 8,295 cirrhotic patients with portal hypertension were enrolled in cohort 1 and 267 patients affected with NCPH were included in cohort 2. MRC was defined as at least two cysts in both kidneys within a patient detected by ultrasonography or computed tomography. Whole-genome sequencing (WGS) was performed in nine patients (four from cohort 1 and five from cohort 2). Then we integrated WGS and publicly available single-cell RNA sequencing (scRNA-seq) to prioritize potential candidate genes. Genes co-expressed with known pathogenic genes within same cell types were likely associated NCPH with MRC.Results: The prevalence of MRC in NCPH patients (19.5%, 52/267) was significantly higher than cirrhotic patients (6.2%, 513/8,295). Further, the clinical characteristics of NCPH patients with MRC were distinguishable from cirrhotic patients, including late-onset, more prominent portal hypertension however having preserved liver functions. In the nine whole genome sequenced patients, we identified three patients with early onset harboring compound rare putative pathogenic variants in the known disease gene PKHD1. For the remaining patients, by assessing cilia genes profile in kidney and liver scRNA-seq data, we identified CRB3 was the most co-expressed gene with PKHD1 that highly expressed in ureteric bud cell, kidney stromal cell and hepatoblasts. Moreover, we found a homozygous variant, CRB3 p.P114L, that caused conformational changes in the evolutional conserved domain, which may associate with NCPH with MRC.Conclusion: ScRNA-seq enables unravelling cell heterogeneity with cell specific gene expression across multiple tissues. With the boosting public accessible scRNA-seq data, we believe our proposed analytical strategy would effectively help disease risk gene identification.

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“…The advent of single cell RNA sequencing (scRNA-seq) allowed a more complete inventory of gene expression profiles within individual neurons, with the expression of "validated cell type genes" used as a framework to identify transcriptionally related neurons [4][5][6][7][8]. Further analysis has revealed novel cell types based on common gene expression, but also that trajectories between cell types to be more gradual and less saltatory than previously appreciated, in part due to transcriptional priming [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Single cell RNA-seq analysis reveals temporally-regulated and quiescence-regulated gene expression in Drosophila larval neuroblasts

et al. 2022

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The mechanisms that generate neural diversity during development remains largely unknown. Here, we use scRNA-seq methodology to discover new features of the Drosophila larval CNS across several key developmental timepoints. We identify multiple progenitor subtypes – both stem cell-like neuroblasts and intermediate progenitors – that change gene expression across larval development, and report on new candidate markers for each class of progenitors. We identify a pool of quiescent neuroblasts in newly hatched larvae and show that they are transcriptionally primed to respond to the insulin signaling pathway to exit from quiescence, including relevant pathway components in the adjacent glial signaling cell type. We identify candidate “temporal transcription factors” (TTFs) that are expressed at different times in progenitor lineages. Our work identifies many cell type specific genes that are candidates for functional roles, and generates new insight into the differentiation trajectory of larval neurons.

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Single-Cell RNA Sequencing of Retina:New Looks for Gene Marker and Old Diseases

Cited by 9 publications

References 63 publications

Definition of the transcriptional units of inherited retinal disease genes by meta-analysis of human retinal transcriptome data

Definition of the transcriptional units of inherited retinal disease genes by meta-analysis of human retinal transcriptome data

Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Single cell RNA-seq analysis reveals temporally-regulated and quiescence-regulated gene expression in Drosophila larval neuroblasts

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