Single-cell Landscape Analysis Reveals HSA21 Induced Regulatory Network in Mammalian Down Syndrome

Down syndrome (DS), characterized by various malfunctions, is the most common genetic chromosomal disorder. As DS population size keeps growing and most of them live beyond their puberty, their early‐onset health problems come into view. However, the molecular alterations have not been thoroughly surveyed before. Here we provide the first description of DS in single-cell resolution, including human and mouse, covering seven different organs. With 71934 mouse cells and 93207 human cells employed, we systematically revealed DS cells, across different cell types and different organs suffering from serious cellular stresses. We observed senescence stresses including ribosomal protein gene accumulation, mitochondrial dysfunction, apoptosis, and sterile inflammation in fetus DS cells. We further raised an HSA21 gene-induced regulatory network driving genome-wide expression alteration. Hence, this study provides valuable information to understand the pathological processes under DS condition. scRNA-seq analysis of aneuploidy (trisomy 21) and diploid fetuses.