Studying Human Development by Single-Cell Profiling of Primary Human Tissues and Genetic Perturbations of Novel Developmental Models

Register in advance for this meeting:

https://ucsd.zoom.us/meeting/register/vJwuceqrpj0jJsgq2LOQaTtv0E7x85Yl3Q   

Friday, April 3, 2020 -
2:00pm to 3:00pm
Zoom
Yan Wu

Recent PhD Grad from the Department of Bioengineering

University of California, San Diego

Studying Human Development by Single-Cell Profiling of Primary Human Tissues and Genetic Perturbations of Novel Developmental Models

Abstract: 

Understanding human development is critical to understanding human evolution, treating developmental disorders, and creating regenerative therapeutics. Single-cell methods have enabled the high-resolution profiling of developmental trajectories and novel organoid models have facilitated a greater understanding of difficult to access developmental periods, especially through the use of perturbation experiments. Here, we used a novel multi-lineage developmental model along with profiling of the developing human prefrontal cortex to better understand human development and evolution. First, we developed a novel visualization method, Similarity Weighted Nonnegative Embedding (SWNE), which both preserves the structure of single-cell datasets and enables key marker genes and relevant genesets to be embedded alongside the cells. We then leveraged a novel multi-lineage developmental model, the teratoma, to study the role of key developmental genes. We conducted a pooled CRISPR knockout screen of those regulators in the teratoma with a single cell RNA-seq readout, enabling us to better understand the function of these genes across all major human lineages. Finally, we used both single-cell RNA-seq and single-cell chromatin accessibility profiling to study the role of human accelerated regions (HARs), genomic regions thought to influence human-specific evolution, in human corticogenesis. The chromatin accessibility enabled us to assess the activity of HARs in specific developmental cell types and link those HARs to genes using co-accessibility of the HARs and gene promoters, while the RNA-seq enabled us to validate the expression of those HAR-linked genes.  

Bio: 
Yan is a recent PhD grad from the Department of Bioengineering who works on developing new computational methods for high-throughput single-cell epigenetic and transcriptomic datasets. Yan uses combines these methods with CRISPR-based genetic perturbations to study human development and disease.