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Great ape organoids to reconstruct uniquely human development

Project description

What sets us apart from our closest evolutionary relatives?

How are Neanderthals and modern humans different? What caused humans to diverge? What separates us from chimpanzees and other apes? Genome comparisons have identified genetic changes that likely contribute to innovations in human metabolic and cognitive physiology. The EU-funded ANTHROPOID project will use organoids to study the changes that set modern humans apart from our closest evolutionary relatives as well as all other organisms on the planet. It will create a great ape developmental cell atlas using cortex, liver and small intestine organoids. The research team will dissect enhancer evolution using single-cell genomic screens and ancestralise human cells to resurrect prehuman cellular phenotypes.

Objective

Humans diverged from our closest living relatives, chimpanzees and other great apes, 6-10 million years ago. Since this divergence, our ancestors acquired genetic changes that enhanced cognition, altered metabolism, and endowed our species with an adaptive capacity to colonize the entire planet and reshape the biosphere. Through genome comparisons between modern humans, Neandertals, chimpanzees and other apes we have identified genetic changes that likely contribute to innovations in human metabolic and cognitive physiology. However, it has been difficult to assess the functional effects of these genetic changes due to the lack of cell culture systems that recapitulate great ape organ complexity. Human and chimpanzee pluripotent stem cells (PSCs) can self-organize into three-dimensional (3D) tissues that recapitulate the morphology, function, and genetic programs controlling organ development. Our vision is to use organoids to study the changes that set modern humans apart from our closest evolutionary relatives as well as all other organisms on the planet. In ANTHROPOID we will generate a great ape developmental cell atlas using cortex, liver, and small intestine organoids. We will use single-cell transcriptomics and chromatin accessibility to identify cell type-specific features of transcriptome divergence at cellular resolution. We will dissect enhancer evolution using single-cell genomic screens and ancestralize human cells to resurrect pre-human cellular phenotypes. ANTHROPOID utilizes quantitative and state-of-the-art methods to explore exciting high-risk questions at multiple branches of the modern human lineage. This project is a ground breaking starting point to replay evolution and tackle the ancient question of what makes us uniquely human?

Coordinator

F. HOFFMANN-LA ROCHE AG
Net EU contribution
€ 1 038 782,71
Address
Grenzacherstrasse 124
4070 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
Other funding
€ 0,00

Beneficiaries (2)