From signals to chromatin: Multi-omics approach in gastruloids to define the code of signals, chromatin, and transcription for embryonic lineage specification

Prof. Dr. Sebastian Arnold (CIBSS AI), Institute of Experimental and Clinical Pharmacology and Toxicology (Faculty of Medicine),  University of Freiburg

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The specification of different cell types from progenitors is regulated by signals, transcriptional programs and underlying chromatin. In the early embryo, first cell lineage decision segregates mesoderm and endoderm (ME) from neuroectoderm (NE). The molecular code of how signals, and transcription factors contribute and act in combination and/or in successive steps on the level of enhancers and chromatin conformation to regulate cell fate programs still remains rather poorly resolved. Within this project we aim to understand how signals, transcriptional programs and chromatin changes are spatiotemporally orchestrated in the embryo. To overcome some of the experimental limitations working with mammalian embryos we employ ESCs-based gastruloids that recapitulate gastrulation stage embryos. We extended the application of gastruloids by generating various ESC lines that harbour either gene-deletions of TFs or dox-inducible expression constructs of TFs and combinations hereof. In addition, ESCs also express membrane-bound fluorescent proteins that allow for tracking of cells. We will use this versatile system to systematically define signalling and TF requirements for specification of different cell lineages, and the effect on lineage specific chromatin changes.