TITLE: “Defining chromatin accessibility and molecular dysregulation in Down Syndrome.”
ABSTRACT: Despite accumulating almost two centuries of medical information, the exact mechanisms underlying Down Syndrome (DS) developmental pathology remain unknown. DS is caused by trisomy of chromosome21 (T21), but without pinpointing the way in which T21 confers molecular dysfunctions and subsequently impairs neurodevelopment, it has been difficult to devise medical interventions that will reduce cognitive deficits. In order to identify these mechanisms in DS and deconvolute the inherent complexity of the developing brain, we are leveraging single cell technologies to contrast DS and healthy expression profiles and chromatin accessibility in midgestation brain tissue and patient-derived primary human neural progenitor cells (phNPCs). Based on previous bulk RNA and chromatin analyses in DS samples and our preliminary data, we anticipate 1) changes in cell composition and 2) altered gene-regulatory networks affecting neurogenesis pathways in neural progenitors, oligodendrocyte precursor cells, and astrocytes. By uncovering these cytological and molecular aberrations, we hope to progress the understanding of neurodevelopment and DS to promote medical advances in the future.
