Poster presentation at the Single Cell Genomics 2022 conference

Abstract

Following gastrulation, the three primary germ layers develop into the major organs in a process known as organogenesis. Single-cell RNA sequencing has enabled the profiling of the gene expression dynamics of these cell fate decisions, yet a comprehensive map of the interplay between transcription factors and cis-regulatory elements is lacking, as are the underlying gene regulatory networks. Here we generate a multi-omics atlas of mouse early organogenesis by simultaneously profiling gene expression and chromatin accessibility from tens of thousands of single cells. We develop a computational method to leverage the multi-modal readouts to predict transcription factor binding events in cis-regulatory elements, which we then use to infer gene regulatory networks that underpin lineage commitment events. Finally, we show that these models can be used to generate in silico predictions of the effect of transcription factor perturbations. We validate this experimentally by showing that Brachyury is essential for the differentiation of neuromesodermal progenitors to somitic mesoderm fate by priming cis-regulatory elements.

Ricard Argelaguet

Computational Biologist

My research interests include statistical methods for multi-modal data integration and single-cell data analysis