DeCoDe Platy · Reconstructing the complete developmental lineage of Platynereis dumerilii
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-07-01 → 2023-06-30
- EU contribution
- €174,806
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Reconstructing the complete developmental lineage of Platynereis dumerilii
Despite their differences in shape, size, and function, all the cells in an animal share the same genome and are created from the same fertilised egg. This incredible diversity of cell types is orchestrated by a complex regulatory apparatus, which guides cell populations towards different fates as development progresses. The mechanisms which change and maintain cell type identity are fundamental for multicellular organisms, shared between species to a remarkable degree, and often dysregulated in ageing or disease. In this project we studied the early development of a marine worm in order to document how cell types emerge and understand the mechanisms that control cellular differentiation. We gathered snapshots of gene expression with single-cell resolution for various time points during development and tried to stitch them together. We intended to supplement this with data of different types that would provide more context, such as the location of the cell types in the body of the developing worm or the characteristic morphology of each cell type. Shortly before the mid-point of the fellowship, the fellow received an offer for a permanent position elsewhere. Considering the precarity of employment in research and higher education the fellow felt compelled to accept the offer, and had to give up the fellowship as a result. Both the fellow and the host remain committed to finishing the project despite the formal interruption of the fellowship, and data acquisition has already restarted in the host lab.
Data: CORDIS, © European Union
Project objective
Cells in multicellular organisms show a huge diversity of shape, size, and function, yet are all descended from the same totipotent zygote. As development progresses, cells lose their ability to contribute to different fates, instead committing to a narrower subset of expression programs. This stepwise reduction of differentiation potential has been illustrated in Waddington’s epigenetic landscape (“Waddington lineage”). The specific gene expression programs of cell types are governed by Core Regulatory Complexes (CoRCs), where transcription factors cooperate to maintain their own expression and the effector genes that give rise to the cellular phenotype. Cell types exist as terminal or transitory states of the Waddington lineage, and it is yet unclear whether and to what extent transitory developmental and terminal cell types involve similar or distinct regulatory principles and effector modules.I will reconstruct the Waddington lineage of Platynereis dumerilii, an indirectly developing marine invertebrate with a wealth of transitory developmental and terminal cell types. I will gather single-cell RNA-seq and chromatin accessibility data for multiple developmental stages and computationally identify putative cell types. I will map these onto locations in the animal body using the in-situ expression patterns of lineage and cell type markers, and exploit unique electron microscopy data to explore the connection between gene expression and subcellular morphology. After connecting successive stages computationally, I will validate the resulting Waddington lineage with functional experiments, disrupting the expression of effector genes in the terminal cell types with CRISPR/Cas9.By combining gene expression, chromatin accessibility, cellular lineage information, functional genomics, spatial localization, and, uniquely, subcellular morphology, we will shed light on animal development and the regulatory mechanisms that govern cell types.
Original text from CORDIS.
Participants
- EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergCoordinatorGermany
Links
Data: CORDIS, © European Union