February 18, 2020
158 Hershey Hall (Grand Salon)
Manu Setty, Ph.D.
Sloan Kettering Institute, New York, NY
"Characterization of lineage decisions in developmental trajectories using single-cell data"
How a cell decides its lineage is a long-standing and enigmatic question in molecular biology. I will present my research to characterize lineage decisions in developmental trajectories by computational modeling of high throughput data such as single-cell RNA-seq. I will describe Palantir, the first single-cell trajectory detection algorithm to model continuities in lineage decisions. Palantir models differentiation as a Markov process to compute the lineage biases and differentiation potential, a measure of plasticity, for all cells. Palantir modeling enables an accurate identification of lineage decision regions and associated gene expression and regulatory dynamics. I will then describe our study to characterize the spatial and temporal trajectories of mouse endoderm development. Combining Palantir modeling with a large-scale single-cell data, we uncovered an unexpected plasticity of embryonic epiblast cells to differentiate to the surrounding extra-embryonic endoderm at implantation and the concomitant emergence of the spatial signal in the endoderm. Our analysis further demonstrated the convergence of embryonic definitive and extra-embryonic visceral endoderm cells into spatially organized organ territories in the gut-tube at mid-gestation.