Exposure of newborns to atmospherically relevant artificial particulate matter induces hematopoietic stem cell senescence

Abstract

Research on the negative impacts of PM_2.5 have been focused on lung, brain, immune, and metabolism-related diseases. However, little is known about the mechanism underlying the effects of PM_2.5 on the modulation of hematopoietic stem cell (HSC) fate. Maturation of the hematopoietic system and differentiation of hematopoietic stem progenitor cells (HSPCs) occurs soon after birth when infants are susceptible to external stresses. We investigated how exposure to atmospherically relevant artificial particulate matter of diameter < 2.5 µm (termed, PM_2.5) affects HSPCs in newborns. The lungs of newborn mice exposed to PM_2.5 exhibited higher levels of oxidative stress and inflammasome activation, which continued during aging. PM_2.5 also stimulated oxidative stress and inflammasome activation in bone marrow (BM). PM_2.5-exposed infant mice at 12 months but not at 6 months displayed progressive senescence of HSCs accompanied by preferential impairment of the BM microenvironment with age-related phenotypes, as evidenced by colony-forming assay and serial transplantation and animal survival experiments. Further, PM_2.5-exposed middle-aged mice did not exhibit radioprotective potential. Collectively, exposure of newborns to PM_2.5 causes progressive senescence of HSCs. These findings revealed a novel mechanism by which PM_2.5 affects the fate of HSCs, highlighting the crucial role of early life exposure to air pollution in determining human health outcomes.