During human development, diverse differentiated cell types emerge from a single pluripotent population of cells. This differentiation process requires mechanisms to activate the target lineages' gene programs and repress those of alternative lineages. However, the underlying functional changes in spatial genome organization accompanying these changes in gene expression are poorly understood, especially during mammalian development.
Our lab is primarily interested in brain development, which begins shortly after gastrulation and continues in the early infant. While this complex process is being investigated in vivo, we focus on in vitro modeling of neurogenesis in 2D and 3D by reprogramming embryonic fibroblasts or induced pluripotent stem cells (iPSCs) to neurons and to brain organoids. Our objective is to understand how changes in genome organization affect expression of gene programs during neurogenesis and other differentiation pathways such as adipogenesis using advanced genomics methods such as ATAC-Seq and HiC-Seq, transcriptomics and metabolomics.
The overarching goal is to provide an ideal system to gain mechanistic insights into regulating early fate commitment during neurogenesis and other differentiation pathways. As neurodevelopmental disorders such as ADHD, autism, learning disabilities, intellectual disability, conduct disorders, cerebral palsy, and impairments in vision and hearing are often caused by misregulated transcriptional pathways our work may provide novel insights into the etiology of diseases.
Learn more about Piergiorgio Percipalle's Laboratory of Cell and Molecular Biology.