Department of Biochemistry and Molecular Biophysics
Columbia University Medical Center
Host: Joe Pickrell
Title: Delineating Neurogenic Commitment with Single Cell Resolution
Abstract: Cellular lineage commitment results from the induction of dynamically regulated transcriptional programs. I will present an unbiased approach to studying neurogenesis that combines temporal single cell RNA-sequencing and topology-based computational analyses. The approach involves a non-linear, model-independent, statistical framework tailored to capture high-dimensional continuous relationships, allowing for the unsupervised characterization of transient cellular states. As a proof of concept, we applied this workflow to the study of mouse embryonic stem cells (mESCs) as they differentiate into motor neurons, in vitro. This work demonstrates our ability to resolve asynchrony and continuity in cellular identity over time, along with the identification of transient cellular states based on dynamic changes in stage-dependent combinations of transcription factors, RNA-binding proteins and long non-coding RNAs.
The approach I will discuss has wide applicability to a broad range of biological problems that involve asynchronous or stochastic cellular responses to developmental cues or environmental perturbations.
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