A cellular-resolution molecular map details how Down syndrome alters human brain development before birth. The study analyzed more than 100,000 nuclei from human prenatal neocortex samples collected across 26 pre-genotyped donors during gestational weeks 13 to 23—the only window during which all the cortical neurons a person will carry for their entire life are generated. The findings suggest that Down syndrome disrupts the developmental sequence of that process, creating shifts that may help explain later differences in cognition, learning, and sensory processing. This work is published in Science in the paper, “A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex.“ “There’s a new level of detail here that had never existed before,” said Luis de la Torre-Ubieta, PhD, an assistant professor of psychiatry and biobehavioral sciences at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “For the first time, we can really try to understand systematically what’s going on in the developing brain of individuals with Down syndrome.” “No one had looked at the developing human brain in Down syndrome directly using single-cell genomics,” he continued. The Down syndrome research field has historically focused on two areas: the adult brain and the disorder’s connection to neurodegeneration. What remained largely unexamined, despite clear indicators that Down syndrome is a developmental condition, was how the condition shapes the developing brain itself. The development of the prenatal neocortex typically follows a tightly orchestrated sequence. Progenitor cells must…
