1.5 IPF
IPF is a deadly respiratory disease that mainly occurs in middle-aged
and elderly people [35]. It is an interstitial disease in which
fibroblast expansion occurs in parallel with excessive production and
deposition of extracellular matrix, leading to airway remodeling,
inflammation, alveolar destruction, and fibrosis [36]. Currently,
many scRNA-seq studies have provided new insights into the cell types
and cell interaction-related biological processes involved in IPF
pathogenesis. Barry R Strip et al. [37] mapped epithelial cell types
in normal and IPF airways by scRNA-seq and revealed the reconstruction
of IPF basal cell diversity. Taylor S. Adams et al. [38] constructed
a single-cell atlas of IPF that focued on aberrant epithelial,
fibroblast,and endothelial cell populations, and identified all known
lung epithelial cell populations in control samples, including alveolar
type 1 (AT1) and type 2 (AT2) cells, ciliated cells, basal cells, goblet
cells, club cells, pulmonary neuroendocrine cells, ionocytes, and 80
aberrant basaloid cells. The occurrence of IPF is closely related to
alveolar epithelial injury. ScRNA-seq of IPF lung tissues revealed that
matrix metalloproteinase 7 (MMP7), integrin αVβ6, cellular senescence,
and epithelial-mesenchymal transition (EMT) abnormal epithelial cells
were highly expressed at the edges of fibroblastic lesions, whereas they
were not present in normal lung tissues, which once again suggests that
the development of IPF is closely related to alveolar epithelial damage.
This is because dysfunctional epithelial cells interact with mesenchymal
cells, immune cells, and endothelial cells via various signaling
mechanisms which trigger the activation of fibroblasts and
myofibroblasts, whereas abnormal NOTCH2+ basal cells are susceptible to
metabolic dysfunction, aberrant epithelial activation, and epithelial
repair dysfunction [39].
Fibroblasts are the central mediators of extracellular matrix production
in IPF. Rebecca Peyser et al. [40] identified 49 signature genes and
delineated fibroblast subpopulations by scRNA-seq techniques. They found
that fibroblast activation was poorly correlated with the expression of
transforming growth factor-β pathway genes. The immune microenvironment
involved in IPF has now been revealed by use of scRNA-seq technology.
Those studies showed that macrophages around the lesion secrete a type 1
phosphorylated protein (SPP1) that causes organ fibrosis, and that the T
cells involved in anti-fibrotic and pro-fibrotic activates are mainly
Th9, Th22, and γδT cells [37]. It is self-evident that fibroblasts,
epithelial cells, and immune cells do not independently influence the
formation and development of IPF. A combination of biological
approaches, as well as in vivo modeling will provide important
data regarding the transcriptomic changes and cellular interactions
associated with IPF development, and those data will need to be further
validated by measurements of gene and protein expression.