The cellular origins and evolution of the maternal-fetal interface in mammals

• Applicants: Professor Dr. Simon Anders; Professor Dr. Henrik Kaessmann, Ph.D.; Professor Dr. Oliver Stegle, Ph.D.
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology)
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433034324

The placenta provides a sophisticated maternal-fetal interface that is key for prenatal development and originated as a completely new organ structure in mammals. It is therefore not only essential for reproduction but also represents an intriguing model for understanding a fundamental biological question: how do new organs arise during evolution? Previous work provided initial insights into the structural evolution of the fetal and maternal placenta and underlying genomic alterations. Nevertheless, on a cellular and regulatory level, the evolution of the placenta and its developmental dynamics across species remain overall little understood. In the proposed project, we will thus unveil the evolution of the placenta by generating comprehensive sets of transcriptome and epigenome data for individual placental cells across pregnancies of humans and seven other representative mammals, leveraging recently developed single-cell genomics approaches. Our principal investigator team consists of an experienced evolutionary genomicist (Kaessmann) and two expert "omics" biostatisticians (Anders, Stegle). Together with our NGS partner, the NCCT, our consortium will ensure efficient data production and state-of-the-art bioinformatics analyses. Our project has two major biological aims. First, we will characterize cellular differentiation paths in the placenta across mammals, in order to understand developmental emergences of placental cell types and interactions required for fetal-maternal cellular communication. We will then compare cellular dynamics across species and identify ancestral cell types as well as novel cell types that emerged during evolution in specific mammalian lineages. Gene expression analyses will reveal activity changes that underlie placentation differences between species. We hypothesize that in addition to expression changes of old genes, the emergence of new genes were key to placental evolution, and that species-specific features of placentation arise late in development. Second, we will elucidate gene regulatory networks that control the cellular development of the fetal-maternal interface in the different species, with a particular focus on cell type-defining transcription factors. Cross-species comparisons will uncover key ancestral and species-specific regulatory aspects of placentation. We will especially contrast the relative contributions of changes of transcription factors and gene-specific regulatory elements (enhancers), respectively, to the phenotypic evolution of the placenta. Altogether, our work will substantially advance our understanding of the cellular origins and evolution of the placenta in mammals and reveal placental features that are crucial for successful pregnancies across species. Our study will thus also provide novel perspectives on the unique reproductive biology of our own species.

• DFG Programme: Research Grants