Single-nucleus chromatin accessibility and RNA sequencing reveal impaired brain development in prenatally e-cigarette exposed neonatal rats
Zhong Chen,
Wanqiu Chen,
Yong Li,
Malcolm Moos, Jr.,
Daliao Xiao,
Charles Wang
Affiliations
Zhong Chen
Center for Genomics, School of Medicine, Loma Linda University, 11021 Campus St., Loma Linda, CA 92350, USA
Wanqiu Chen
Center for Genomics, School of Medicine, Loma Linda University, 11021 Campus St., Loma Linda, CA 92350, USA
Yong Li
Lawrence D. Longo, MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
Malcolm Moos, Jr.
Center for Biologics Evaluation and Research & Division of Cellular and Gene Therapies, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA
Daliao Xiao
Lawrence D. Longo, MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA; Corresponding author
Charles Wang
Center for Genomics, School of Medicine, Loma Linda University, 11021 Campus St., Loma Linda, CA 92350, USA; Division of Microbiology & Molecular Genetics, Department of Basic Science, School of Medicine, Loma Linda University, 11021 Campus St., Loma Linda, CA 92350, USA; Corresponding author
Summary: Although emerging evidence reveals that vaping alters the function of the central nervous system, the effects of maternal vaping on offspring brain development remain elusive. Using a well-established in utero exposure model, we performed single-nucleus ATAC-seq (snATAC-seq) and RNA sequencing (snRNA-seq) on prenatally e-cigarette-exposed rat brains. We found that maternal vaping distorted neuronal lineage differentiation in the neonatal brain by promoting excitatory neurons and inhibiting lateral ganglionic eminence-derived inhibitory neuronal differentiation. Moreover, maternal vaping disrupted calcium homeostasis, induced microglia cell death, and elevated susceptibility to cerebral ischemic injury in the developing brain of offspring. Our results suggest that the aberrant calcium signaling, diminished microglial population, and impaired microglia-neuron interaction may all contribute to the underlying mechanisms by which prenatal e-cigarette exposure impairs neonatal rat brain development. Our findings raise the concern that maternal vaping may cause adverse long-term brain damage to the offspring.
