Introduction
Single-cell sequencing (SCS) is an emerging technology used to
understand the function and gene expression status of individual cells,
as well as interactions that occur at the single-cell level by use of
single-cell suspensions, preparations, single-cell capture and labeling
methods, library preparation and sequencing, and data analysis [1].
Currently, SCS technologies have been used in genome sequencing
(scDNA-seq), transcriptome sequencing (scRNA-seq), DNA methylation
sequencing, histone modification sequencing, and chromatin structure
sequencing (scATAC-seq). SCS studies conducted on heterogeneous diseases
have demonstrated significant advantages when compared to studies
conducted using traditional sequencing methods [1, 2]. For instance,
SCS technology has been widely used in the field of upper and lower
airway diseases, such as inflammatory diseases, viral infections, and
cancers [3]. Moreover, it can be used to identify rare subgroups,
circulating inflammatory cells, tumor or immune microenvironments,
cancer stem cells, and to classifry the heterogeneity and molecular
subtypes of airway inflammations and tumors[4]. Futhermore, SCS can
be used to study various mechanisms associated with disease onset,
progression, tumor metastasis, evolution, relapse, and treatment
resistance. Here we provide a systematic review of current advances in
the application of several common SCS techniques in the upper and lower
airways.
1. SCS in airway inflammatory
diseases
The upper and lower inflammatory airway diseases discussed in this
review are allergic rhinitis (AR), chronic rhinosinusitis (CRS),
bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and
idiopathic pulmonary fibrosis (IPF). These diseases are characterized by
pathological features such as luminal inflammation, epithelial chemosis
and hyperplasia of the basement membrane, smooth muscle and submucosal
cells, as well as glandular hyperplasia. Their common features are
epithelial barrier dysfunction, including defective tight junctions
(TJs) between cells and increased epithelial permeability. ScRNA-seq is
widely used in the field of immune diseases due to its advantages of
high cell throughput, low cost of library construction, and short
capture cycle. At present, scRNA-seq studies of upper and lower airway
diseases have revealed that the airway has a complex structure and
contains multiple cell types, such as epithelial cells that act as a
barrier, and immune cells for antimicrobial defense. ScRNA-seq is also
used to understand airway biology, disease pathogenesis, and disease
progression between the upper and lower inflammatory airways. Here, we
discuss the use of single cell sequencing in several different airway
inflammatory diseases on individual basis.