Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

Korrapati, Soumya; Taukulis, Ian; Olszewski, Rafal T.; Pyle, Madeline; Gu, Shoujun; Singh, Riya; Griffiths, C. M.; Martin, Daniel; Boger, Erich T.; Morell, Robert J.; Hoa, Michael

doi:10.3389/fnmol.2019.00316

Cited by 77 publications

(139 citation statements)

References 139 publications

(181 reference statements)

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“…Regulatory network inference. Gene regulatory network inference using single cell regulatory network inference and clustering (SCENIC) has been previously described 2,31 . It is a computational method for inferring GRN based on the expression level of transcriptional factors and their conserved motif-enriched cis-regulatory sequences.…”

Section: Differential Expression (De) Analysismentioning

confidence: 99%

“…Gene ontology analyses and gene enrichment analyses were performed using Enrichr (https ://amp.pharm .mssm.edu/Enric hr/) as previously described 2,[88][89][90][91] . The combined score approach where enrichment score is calculated from the combination of the p-value computed using the Fisher exact test and the z-score was utilized.…”

Section: Gene Ontology and Gene-set Enrichment Analysismentioning

confidence: 99%

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Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

Olszewski

Taukulis

et al. 2020

Sci Rep

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The stria vascularis (SV) in the cochlea generates and maintains the endocochlear potential, thereby playing a pivotal role in normal hearing. Knowing transcriptional profiles and gene regulatory networks of SV cell types establishes a basis for studying the mechanism underlying SV-related hearing loss. While we have previously characterized the expression profiles of major SV cell types in the adult mouse, transcriptional profiles of rare SV cell types remained elusive due to the limitation of cell capture in single-cell RNA-Seq. The role of these rare cell types in the homeostatic function of the adult SV remain largely undefined. In this study, we performed single-nucleus RNA-Seq on the adult mouse SV in conjunction with sample preservation treatments during the isolation steps. We distinguish rare SV cell types, including spindle cells and root cells, from other cell types, and characterize their transcriptional profiles. Furthermore, we also identify and validate novel specific markers for these rare SV cell types. Finally, we identify homeostatic gene regulatory networks within spindle and root cells, establishing a basis for understanding the functional roles of these cells in hearing. These novel findings will provide new insights for future work in SV-related hearing loss and hearing fluctuation.

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Section: Differential Expression (De) Analysismentioning

confidence: 99%

Section: Gene Ontology and Gene-set Enrichment Analysismentioning

confidence: 99%

Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

Olszewski

Taukulis

et al. 2020

Sci Rep

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“…High-profile, hearingrelated datasets have been made available in the gEAR even before publication, and links to gEAR as the primary method for accessing datasets are ubiquitous within talks/posters at professional conferences. Additionally, the gEAR has already been used for data dissemination 5,[23][24][25][26][27][28][29][30][31][32][33][34][35] , hypothesis generation [36][37][38][39][40][41][42][43][44] and validation of gene expression 29,30,[45][46][47][48][49][50][51][52][53][54][55][56][57] by numerous publications in the ear field. It has also been referenced by numerous groups as a useful tool [58][59][60][61][62][63][64] .…”

Section: Discussionmentioning

confidence: 99%

gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

Orvis

Gottfried

Kancherla

et al. 2020

Preprint

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The gEAR portal (gene Expression Analysis Resource, umgear.org) is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing. The gEAR supports visualization of multiple RNA-seq data types (bulk, sorted, single cell/nucleus) and epigenomics data, from multiple species, time points and tissues in a single-page, user-friendly browsable format. An integrated scRNA-seq workbench provides access to raw data of scRNA-seq datasets for de novo analysis, as well as marker-gene and cluster comparisons of pre-assigned clusters. Users can upload, view, analyze and privately share their own data in the context of previously published datasets. Short, permanent URLs can be generated for dissemination of individual or collections of datasets in published manuscripts. While the gEAR is currently curated for auditory research with over 90 high-value datasets organized in thematic profiles, the gEAR also supports the BRAIN initiative (via nemoanalytics.org) and is easily adaptable for other research domains.

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“…The stria vascularis plays an important role in maintaining the cochlear endolymphatic potentials (EP) which is essential for the mechanical electrical conduction of the hair cells [25][26][27][28][29]. The stria vascularis is composed with the macrophage-like melanocytes, which also called the intermediate cells [28,30,31].…”

Section: Introductionmentioning

confidence: 99%

Transcript Profiles of Stria Vascularis in Models of Waardenburg Syndrome

et al. 2020

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Background. Waardenburg syndrome is an uncommon genetic condition characterized by at least some degree of congenital hearing loss and pigmentation deficiencies. However, the genetic pathway affecting the development of stria vascularis is not fully illustrated. Methods. The transcript profile of stria vascularis of Waardenburg syndrome was studied using Mitf-M mutant pig and mice models. Therefore, GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation. Results. There were 113 genes in tyrosine metabolism, melanin formation, and ion transportations showed significant changes in pig models and 191 genes in mice models. In addition, there were some spice’s specific gene changes in the stria vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19, and Cdh24 genes, were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the stria vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1, and Col11a2 genes were higher, and the expression of Col8a2, Cd34, and Ncam genes were lower in the porcine models compared to mouse models. Conclusions. Our data suggests that there is a significant difference on the gene expression and function between these two models.

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Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

Cited by 77 publications

References 139 publications

Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

Transcript Profiles of Stria Vascularis in Models of Waardenburg Syndrome

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