Human organoids hold huge potential for future biomedical applications. To demonstrate the feasibility and utility of combining human organoids with single-cell technology, an Organoid Cell Atlas pilot project has been launched.
Human organoids are three-dimensional structures of cultured cells that recapitulate important aspects of in vivo organ development and biological function. They provide tractable in vitro models of human physiology and pathology. As a result, they can enable international studies that are often difficult or impossible to conduct in human subjects. Human organoids complement and, in the future, may replace animal models in many areas of preclinical drug development. They also show promise in contributing to regenerative medicine, with the long-term goal of producing functional biological structures that can be used for transplantation.
Despite their promise, several key challenges remain regarding human organoids. The most important challenge is the need for better characterisation and validation of organoids as faithful models of human biology. Additionally, a future catalogue of well-characterised human organoids needs to include extensive replication, to quantify sources of technical and biological variation. Finally, the inclusion of genetically diverse sample donors will be important to assess interindividual variation within the population.
While current organoid protocols are useful for some applications, they have several technical and conceptual limitations. It will be key to develop robust protocols that yield organoids with adequate tissue organisation, differentiated cells, vascularisation, immune cell infiltration and even a microbiome. Single-cell sequencing and spatial profiling have a key role in addressing some of these current issues.
The Organoid Cell Atlas
The Organoid Cell Atlas is a pilot project within the Human Cell Atlas, focussing on the single-cell characterisation of organoids and complex in vitro systems. Described in Nature Biotechnology, the project will facilitate the production, quality control, dissemination and utilisation of single-cell and spatial genomics data for human organoids. It will also aim to link such datasets to the comprehensive profiles of primary tissues that are being generated within the Human Cell Atlas.
The Human Organoid Cell Atlas is an open, collaborative network that aims to pursue four complementary direction:
- Encourage and standardise single-cell profiling of human organoids
- Facilitate access to single-cell organoid data (and informative metadata) through the Human Cell Atlas data infrastructure
- Establish computational methods and tools for connecting organoid profiles with primary tissue data
- Put organoids into their biological context using the Human Cell Atlas profiles of their in vivo counterparts
The data integration will be driven by an interactive, openly accessible, web-based computational platform known as the Organoid Cell Atlas Portal. This Portal will build on and extend the existing Human Cell Atlas data infrastructure.
A step towards the Organoid Cell Atlas was recently funded by the European Union Horizon 2020 with the ‘HCA|Organoid’ project. In this pilot project, researchers are generating single-cell transcriptome profiles, epigenome maps and detailed imaging data in a selection of human organoids (colon and brain).
In vitro models, such as organoids, will complement the ongoing efforts of the Human Cell Atlas by enabling researchers to functionally dissect and systematically perturb human biological systems. By creating an open and inclusive research environment that facilitates collaboration, the Organoid Cell Atlas specifically aims to advance biomedical discovery and support the development of regenerative therapies.