Summary
Trisomy 21 (T21) is the most prevalent chromosomal abnormality worldwide, with an incidence of approximately 1 in 700 live births. Our single cell RNAseq data and immunofluorescent stainings have demonstrated upregulation of the surfactant metabolism pathway and increased cell number of differentiated proximal airway markers (SCGB1A1 and FOXJ1), suggesting precocious development/differentiation in the T21 lungs, which may be associated to genome wide perturbation due to dysregulated epigenetic regulation. In this proposal we will assess the ontogeny of pulmonary anomalies observed in Down Syndrome (DS) by using single nuclear (sn) RNA and snATAC sequencing (multiome sequencing) to simultaneously assess the epigenetic landscape and determine the cellular and molecular abnormalities observed in developing T21 lungs (from prenatal to postnatal), which may ultimately provide a foundation for potentially new therapies for compromised lungs in individuals with DS.