Applications of single‐cell sequencing for the field of otolaryngology: A contemporary review

Abstract

ObjectivesSingle‐cell RNA sequencing (scRNA‐Seq) is a new technique used to interrogate the transcriptome of individual cells within native tissues that have already resulted in key discoveries in auditory basic science research. Rapid advances in scRNA‐Seq make it likely that it will soon be translated into clinical medicine. The goal of this review is to inspire the use of scRNA‐Seq in otolaryngology by giving examples of how it can be applied to patient samples and how this information can be used clinically.MethodsStudies were selected based on the scientific quality and relevance to scRNA‐Seq. In addition to mouse auditory system (inner ear including hair cells and supporting cells, spiral ganglion neurons, and inner ear organoids), recent studies using human primary cell samples are discussed. We also perform our own analysis on publicly available, published scRNA‐Seq data from oral head and neck squamous cell carcinoma (HNSCC) samples to serve as an example of a clinically relevant application of scRNA‐Seq.ResultsStudies focusing on patient tissues show that scRNA‐Seq reveals tissue heterogeneity and rare‐cell types responsible for disease pathogenesis. The heterogeneity detected by scRNA‐Seq can result in both the identification of known or novel disease biomarkers and drug targets. Our analysis of HNSCC data gives an example for how otolaryngologists can use scRNA‐Seq for clinical use.ConclusionsAlthough there are limitations to the translation of scRNA‐Seq to the clinic, we show that its use in otolaryngology can give physicians insight into the tissue heterogeneity within their patient's diseased tissue giving them information on disease pathogenesis, novel disease biomarkers or druggable targets, and aid in selecting patient‐specific drug cocktails.

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

“…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] . Our team screens the literature on a regular basis, uploads and curates new datasets relevant to the hearing research community, and has thereby transformed the gEAR from a simple tool to a high value resource.…”

Single‐cell RNA sequencing in oral science: Current awareness and perspectives

“…87,[89][90][91] Using known markers of CSCs, 92 the presence of CSCs was validated in scRNA-Seq data. 93 Mediator Complex Subunit 28 (MED28) was detected as DEG F I G U R E 3 Illustration for key findings of OSCC through by scRNA-seq. (A) The heterogeneity of malignant cells revealed by scRNA-seq.…”

“…CSCs have been dissected by scRNA‐seq in a few types of cancers 87,89–91 . Using known markers of CSCs, 92 the presence of CSCs was validated in scRNA‐Seq data 93 . Mediator Complex Subunit 28 (MED28) was detected as DEG of OSCC by scRNA‐seq, upregulation of which was reported to increase the OSCC stem‐cell like activity 94 .…”

“… 87 , 89 , 90 , 91 Using known markers of CSCs, 92 the presence of CSCs was validated in scRNA‐Seq data. 93 Mediator Complex Subunit 28 (MED28) was detected as DEG of OSCC by scRNA‐seq, upregulation of which was reported to increase the OSCC stem‐cell like activity. 94 Seventy‐four genes with significantly higher expression in breast cancer stem cells than in non‐CSCs were identified by scRNA‐seq, many of which were not markers of breast cancer, consistent with the idea that there is a shared expression profile among the CSCs from different cancers.…”

Current Insights and Advancements in Head and Neck Cancer: Emerging Biomarkers and Therapeutics with Cues from Single Cell and 3D Model Omics Profiling

“…6) Looking for genetic targets of FDA-approved drugs or small molecules in clusters of malignant sub-populations or TME cells can help identifying new druggable targets. A new database called Pharos describes 20,000 gene/protein targets and the drugs molecules available which can be further repurposed for use in HNC treatment (67). Some bioinformatics studies have gone beyond biomarker discovery and cellular heterogeneity.…”