%0 Journal Article
%T PM2.5 induces a senescent state in mouse AT2 cells.
%A Cheng P
%A Chen Y
%A Wang J
%A Han Z
%A Hao 
%A Li Y
%A Feng F
%A Duan X
%A Chen H
%J Environ Pollut
%V 347
%N 0
%D 2024 Apr 15
%M 38431248
%F 9.988
%R 10.1016/j.envpol.2024.123686
%X PM2.5 is known to induce lung injury, but its toxic effects on lung regenerative machinery and the underlying mechanisms remain unknown. In this study, primary mouse alveolar type 2 (AT2) cells, considered stem cells in the gas-exchange barrier, were sorted using fluorescence-activated cell sorting. By developing microfluidic technology with constricted microchannels, we observed that both passage time and impedance opacities of mouse AT2 cells were reduced after PM2.5, indicating that PM2.5 induced a more deformable mechanical property and a higher membrane permeability. In vitro organoid cultures of primary mouse AT2 cells indicated that PM2.5 is able to impair the proliferative potential and self-renewal capacity of AT2 cells but does not affect AT1 differentiation. Furthermore, cell senescence biomarkers, p53 and γ-H2A.X at protein levels, P16ink4a and P21 at mRNA levels were increased in primary mouse AT2 cells after PM2.5 stimulations as shown by immunofluorescent staining and quantitative PCR analysis. Using several advanced single-cell technologies, this study sheds light on new mechanisms of the cytotoxic effects of atmospheric fine particulate matter on lung stem cell behavior.