How do cells form an embryo: Intracellular, temporal, and phenotypic dissection of mammalian gastrulation

Projektbeschreibung

Einblicke in Diversifizierung embryonaler Zellen

In mehrzelligen Organismen bestehen die Zellen aus identischem genetischem Material, weisen aber eine bemerkenswerte Vielfalt auf. Dies zeigt sich anhand der Entwicklung einer einzigen befruchteten Eizelle zu einem komplexen Embryo. Das Ziel des ERC-finanzierten Projekts EmbryoCellEnsemble besteht darin aufzudecken, wie die koordinierte Differenzierung während der Gastrulation bei Säugetieren entsteht. Die Forscherinnen und Forscher werden die parallele und konvergente Differenzierung in embryonalen und extraembryonalen Linien bei Maus und Kaninchen unter Einsatz von Transkriptomik und Epigenomik analysieren. Zudem werden sie epigenetische Mechanismen untersuchen, die Zellzustände etablieren und aufrechterhalten, und die extrazellulären Signale kartieren, die die räumliche 3D-Spezifikation steuern. Die Arbeit wird mechanistische Modelle mit weitreichenden Auswirkungen auf die regenerative Medizin, Krebs und die synthetische Embryogenese liefern.

Ziel

In multicellular orIn multicellular organisms, how variation is achieved while cells comprise identical genetic information represents a fundamental open challenge my group strives to engage in the coming years. The development of a single fertilized egg into a complete embryo represents an especially beautiful embodiment of this problem. The process of differentiation is defined by the capacity of the cell ensemble to acquire increasingly more specialized internal states in a coordinated fashion. We are therefore excited by recent breakthroughs in single-cell transcriptomics and epigenomics since these can capture the emergence of embryonic cellular diversification at incredible resolution. But, we believe there is an urgent need in the field to match descriptive single cell atlases with models and experimental frameworks to derive novel understanding of function and regulation in this process.
To this end, we will undertake three complementary approaches all implemented during specification of the basic mammalian body plan (gastrulation) in vivo. (i) We will scrutinize parallel and converged differentiation in embryonic and extraembryonic lineages at absolute time. This will be achieved in both mouse and rabbit, providing unprecedented molecular insight into the evolutionary hourglass theory. (ii) Building on our recently developed capabilities, we will systematically dissect epigenetic mechanisms shaping and memorizing intracellular states. Importantly, we will do so by controlling for cell type and effects that propagate in and between tissues over time. (iii) Finally, we will chart and manipulate extracellular signaling affecting cell specification in the 3D embryonic space. Our study will provide mechanistic understanding and much-needed quantitative models that truly represent embryonic development as a concurrent interacting ensemble with far-reaching implications for other fields, such as regenerative medicine, cancer, aging, and synthetic embryogenesis.