Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution

Abstract

Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.

Using single-nucleus RNA-sequencing to interrogate transcriptomic profiles of archived human pancreatic islets

“…To overcome these limitations [31], single-nucleus RNA-sequencing (snRNA-seq) has been employed in studies on tissues composed of diverse cell types, including the brain [33,34], kidney [35][36][37], heart [38], skeletal muscle [39,40], stria vascularis [41], retina [42], liver [43,44], lung [45], or white [46,47] and brown adipose tissue [48,49] obtained from mice or human donors. Here, we report a side-by-side comparison between snRNA-seq and scRNA-seq to validate the robustness of the former as an alternative sequencing strategy.…”

Genetic and Lifestyle-Related Factors Influencing Serum Hyper-Propionylcarnitine Concentrations and Their Association with Metabolic Syndrome and Cardiovascular Disease Risk

“…In this study, we found that several genetic variants interacted with each other, including MCTP1_rs4290997, KIF7_rs2350480, F2_rs2070850, PEX3_rs223231, TBC1D22A_rs910543, and PLA2G4C_rs7252136. MCTP1 is a marker for macrophage-1, which may have implications for immunity [25]; PEX3 is related to oxidative stress [26]; F2 is linked to diabetic conditions [27]; PLA2G4C plays a role in the hydrolysis of membrane phospholipids, specifically phosphatidylcholine, which can affect inflammation and MetS [28]. TBC1D22A is involved in cellular processes related to intracellular trafficking and the regulation of cellular metabolism, although research in the context of MetS is limited.…”

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

“…Nowadays, there are several scientific research methods and several technologies are being developed. Some emerging research methods can be introduced into the study of adipose tissue, such as the three-dimensional genome of adipocytes and single-cell multi-omics sequencing, to discover more functional genes that play a role in the function of adipose tissue [123][124][125]. In addition, in recent years, tRNA-derived RNA fragments and piRNAs in ncRNAs have also attracted the attention of researchers [126,127], and their roles in adipose tissue are still worthy of our attention and exploration.…”