Agenda:
David Cacchiarelli (HFSP Fellow, Broad Institute)
"Role of coding and non-coding RNAs in muscle differentiation and disease"
Cole Trapnell (Post Doctoral Fellow, J. Rinn Lab)
"The dynamics of cell fate decisions are revealed by pseudo-temporal ordering of single cells"
Abstract:
Defining the transcriptional dynamics of a temporal process such as cell differentiation is challenging owing to the high variability in gene expression between individual cells. Time-series gene expression analyses of bulk cells have difficulty distinguishing early and late phases of a transcriptional cascade or identifying rare sub-populations of cells, and single-cell proteomic methods rely on a priori knowledge of key distinguishing markers1. Here we describe Monocle, an unsupervised algorithm that increases the temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points. Applied to the differentiation of primary human myoblasts, Monocle revealed switch-like changes in expression of key regulatory factors, sequential waves of gene regulation, and expression of regulators that were not known to have a role in differentiation. We validated some of these predicted regulators in a loss-of function screen. Monocle can in principle be used to recover single-cell gene expression kinetics from a wide array of cellular processes, including differentiation, proliferation and oncogenic transformation.
Food and beverage will be provided at the meeting.
Faculty organizers: Peter Kharchenko and Lev Silberstein