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

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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)