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Article

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

1
Department of Child Health, School of Medicine, University of Missouri, Columbia, MO 65211, USA
2
Department of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
3
Kite Pharma, Santa Monica, CA 90404, USA
4
Informatics Research Core Facility, Life Sciences Center, Missouri School, Columbia, MO 65211, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 261; https://doi.org/10.3390/ijms22010261
Received: 4 November 2020 / Revised: 22 November 2020 / Accepted: 24 December 2020 / Published: 29 December 2020
(This article belongs to the Special Issue Genetic Markers in Sleep Disorders)
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. View Full-Text
Keywords: intermittent hypoxia; sleep apnea; OSA; single cell; snRNA-seq; bulk RNA-seq; deconvolution intermittent hypoxia; sleep apnea; OSA; single cell; snRNA-seq; bulk RNA-seq; deconvolution
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MDPI and ACS Style

Khalyfa, A.; Warren, W.; Andrade, J.; Bottoms, C.A.; Rice, E.S.; Cortese, R.; Kheirandish-Gozal, L.; Gozal, D. Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution. Int. J. Mol. Sci. 2021, 22, 261. https://doi.org/10.3390/ijms22010261

AMA Style

Khalyfa A, Warren W, Andrade J, Bottoms CA, Rice ES, Cortese R, Kheirandish-Gozal L, Gozal D. Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution. International Journal of Molecular Sciences. 2021; 22(1):261. https://doi.org/10.3390/ijms22010261

Chicago/Turabian Style

Khalyfa, Abdelnaby, Wesley Warren, Jorge Andrade, Christopher A. Bottoms, Edward S. Rice, Rene Cortese, Leila Kheirandish-Gozal, and David Gozal. 2021. "Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution" International Journal of Molecular Sciences 22, no. 1: 261. https://doi.org/10.3390/ijms22010261

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