The advent of single cell RNA-Sequencing (RNA-Seq) technology has enabled transcriptome profiling of individual cells. deviations have developed. Located bilaterally at the carotid artery bifurcations, the carotid body (CB) is the predominant sensor for sensing and adjusting acute hypoxemia (Gonzalez, et al., 1994, Lopez-Barneo, et al., 2016, Prabhakar, 2013). This pair of neural crest-derived sensory organs is not only remarkably small but also complicated in structure. As an arterial chemoreceptor, the CB is usually highly vascularized and receives dense innervations. Two major cell types are present in the CB, with neuron-like glomus cells enveloped by supporting sustentacular cells. The glomus cells can instantly depolarize and release neurotransmitters in response to even a moderate drop in oxygen tension, activating afferent nerve fibers that relay information to the brainstem to increase ventilation and sympathetic outflow (Kumar, 2009, Kumar and Prabhakar, 2012). While the CB was discovered almost a century ago, much of the knowledge on glomus cell Araloside X properties was characterized in the past few decades, thanks in part to techniques such as patch-clamp that permitted physiological experiments on individual glomus cells. Majority of these studies were physiology- or pharmacology-based and generated important discoveries that became the foundation for the membrane theory: CB glomus cells express oxygen-sensitive potassium channels and voltage-dependent calcium channels that cause depolarization and neurotransmitter release (Buckler and Vaughan-Jones, 1994, Duchen, et al., 1988, Lahiri, et al., 2006, Lopez-Barneo, et al., 1988, Shimoda and Polak, 2011, Urena, et al., 1994). However, these membrane channels alone do not suffice to explain the upstream oxygen-sensing process. Researchers are now also employing a genetic approach to study genes encoding candidate oxygen sensors by characterizing corresponding knockout mice. This pattern has led to several impactful publications in the past few years, each illustrating different mechanisms of oxygen sensing. (Chang, et al., 2015, Fernandez-Aguera, et al., 2015, Peng, PPIA et al., 2010, Yuan, et al., 2015). Solely relying on physiology or pharmacology experiments offers limited new and unbiased information when selecting candidate genes, yet traditional biochemical or molecular experiments are difficult to perform on CB due to its small size and heterogeneity. The introduction of single cell RNA-Sequencing (RNA-Seq) technology provides a new avenue of opportunities towards understanding the transcriptome profile of CB glomus cells. By creating a list of genes abundantly and/or specifically expressed in these cells, Araloside X it serves as a relatively unbiased resource for mining candidates of the oxygen-sensing apparatus. Similarly, this approach could also be applied to other oxygen-sensing cells, often existing in small quantity or are relatively inaccessible, such as the aortic body, the pulmonary arterial easy muscle cells, the pulmonary neuroepithelial body, the neonatal adrenal medulla, and even an unexpected organ such as the olfactory epithelium. The purpose of this review is to highlight the basic concept of single cell RNA-Seq technology and its recent development. More importantly, we will discuss its recent applications to the field of oxygen-sensing cells to generate new insights and how it can be used in the future to answer additional questions. Single cell RNA-Seq technology Soon after the introduction of next-generation sequencing technology, it was quickly adapted to profile single cell transcriptome by modifying previous single cell transcriptome amplification Araloside X protocols used for single cell qPCR and microarray (Tang, et al., 2009). The single cell RNA-Seq approach circumvents the application limitation (small input RNA) posed by conventional RNA-Seq and carried over many of its advantages (Wang, et al., 2009). It offers nucleotide-resolution accuracy with high sensitivity and a wide dynamic range, allowing better quantification of mRNA transcripts, identifications of splice isoforms and allelic expression patterns. Without the need to predefine hybridization probes, it also enables discovery of novel transcripts. The ability to profile the transcriptome of a single cell broke the bottleneck for many rare cell types. Many functionally important cell types are often located within complex structure or are scarcely available, such as specific subtypes of neurons or early embryonic cells. It was traditionally difficult to characterize the transcriptional features of such cells in a high-throughput manner or without contamination from nearby tissues. By applying single cell RNA-Seq to a wide variety of cells, we gained new knowledge on potential molecular players without being biased by a preformed hypothesis. Also, as more single cells are being sequenced, new revelations of previously.