Periodic Reporting for period 2 - HCA Organoid (HCA|Organoid: Pilot action to establish a multi-tissue human organoid platform within the Human Cell Atlas as a booster of future disease-centric, mechanistic, and translational research)
Periodo di rendicontazione: 2021-01-01 al 2022-09-30
The HCA|Organoid is a European research project which establishes an open access “Organoid Cell Atlas” within the global Human Cell Atlas (HCA) initiative by combining single-cell profiling and organoid technology.
Single-cell profiling enables the creation of a comprehensive reference map of the types and properties of all cells and cell types within the human body. Such a resource will provide a fundamentally new perspective for understanding biology, with profound potential to drive therapeutic advances and accelerate precision and regenerative medicine. In order to streamline research endeavors worldwide, the Human Cell Atlas (HCA) provides global coordination and serves as a comprehensive reference map of the types and properties of all human cells and cell types. Within the global context provided by the HCA, the European research project HCA│Organoid has set out to establish an “Organoid Cell Atlas”. Organoids are tiny, three-dimensional tissue cultures that recapitulate organ development. They can be derived from stem cells – cells that can indefinitely differentiate into various cell types. Resembling miniature versions of potentially any organ or tissue in our body, organoids help us to better understand the complex, three-dimensional microanatomy of an organ. Using organoids has tremendous potential for biomedical applications, since they enable us to assess, intervene and manipulate processes in human organ systems that are otherwise difficult or impossible to conduct in human beings.
Setting up the first version of an atlas of organoid cells, HCA|Organoid is complementing the descriptive nature of a single-cell atlas comprising all human cells/tissues by providing the corresponding atlas for organoids, which is a technology that make human tissue amenable to functional studies and faithful disease modelling in vitro. Toward realizing this vision, HCA|Organoid initially focused on establishing single-cell profiles of human organoids and matched primary tissue from healthy donors. The project derived and comprehensively characterized human brain and colon organoids from nearly 100 individuals each. This resource will enable future discovery-driven and translational research on rare genetic diseases, complex multifactorial diseases, and on cancer. Moreover, HCA|Organoid is establishing a multi‐tissue human organoid platform comprising a “living biobank” and a HCA|Organoid Data Portal for data sharing and user‐friendly analysis. Consequently, the results obtained by the HCA|Organoid project do significantly enhance our understanding of the molecular basis of our cells, ultimately resulting in a deeper understanding of the mechanisms underlying human health and disease.
Single-cell profiling enables the creation of a comprehensive reference map of the types and properties of all cells and cell types within the human body. Such a resource will provide a fundamentally new perspective for understanding biology, with profound potential to drive therapeutic advances and accelerate precision and regenerative medicine. In order to streamline research endeavors worldwide, the Human Cell Atlas (HCA) provides global coordination and serves as a comprehensive reference map of the types and properties of all human cells and cell types. Within the global context provided by the HCA, the European research project HCA│Organoid has set out to establish an “Organoid Cell Atlas”. Organoids are tiny, three-dimensional tissue cultures that recapitulate organ development. They can be derived from stem cells – cells that can indefinitely differentiate into various cell types. Resembling miniature versions of potentially any organ or tissue in our body, organoids help us to better understand the complex, three-dimensional microanatomy of an organ. Using organoids has tremendous potential for biomedical applications, since they enable us to assess, intervene and manipulate processes in human organ systems that are otherwise difficult or impossible to conduct in human beings.
Setting up the first version of an atlas of organoid cells, HCA|Organoid is complementing the descriptive nature of a single-cell atlas comprising all human cells/tissues by providing the corresponding atlas for organoids, which is a technology that make human tissue amenable to functional studies and faithful disease modelling in vitro. Toward realizing this vision, HCA|Organoid initially focused on establishing single-cell profiles of human organoids and matched primary tissue from healthy donors. The project derived and comprehensively characterized human brain and colon organoids from nearly 100 individuals each. This resource will enable future discovery-driven and translational research on rare genetic diseases, complex multifactorial diseases, and on cancer. Moreover, HCA|Organoid is establishing a multi‐tissue human organoid platform comprising a “living biobank” and a HCA|Organoid Data Portal for data sharing and user‐friendly analysis. Consequently, the results obtained by the HCA|Organoid project do significantly enhance our understanding of the molecular basis of our cells, ultimately resulting in a deeper understanding of the mechanisms underlying human health and disease.
In order to lay the foundations of the first "Organoid Cell Atlas" the HCA|Organoid research team established a sharable organoid resource for colon and brain organoids comprising organoids of about 100 individuals each. This organoid resource is available as sharable “living biobank” for the colon and as precise protocols for brain organoid derivation from biobanked stem cells. Profiling work on the single-cell sequencing level was performed for all organoids derived within the project and for a subset single-cell imaging datasets were generated.
The in-depth processing and analysis of the single-cell data is ongoing and follows workflows that will allow rapid, seamless deposition and dissemination of raw data and analysis results from HCA|Organoid and beyond. Moreover, HCA|Organoid worked together with the HCA Data Coordination Platform (HCA-DCP) to include and adapt HCA-DCP metadata standards covering organoid data. This ensures long-term sustainability of the outputs from the HCA|Organoid project because data can be deposited using standard organoid workflows even after the project has ended, and those data have long term archival support as part of the HCA-DCP. In addition, the HCA|Organoid Data Portal will serve as an interactive portal for user-friendly access to organoid data. The final version of the HCA|Organoid Data Portal (https://portal.hca-organoid.eu/(si apre in una nuova finestra)) will display the comprehensive single-cell data as soon as initial processing and data mining of the full single-cell sequencing data set is completed. Moreover, the partners of HCA|Organoid are actively contributing to the HCA strategy and coordination and will continue to disseminate HCA|Organoid results as part of the HCA Biological Network “Organoid”. The HCA|Organoid project website (https://hca-organoid.eu(si apre in una nuova finestra)) and the twitter account (https://twitter.com/OrganoidAtlas(si apre in una nuova finestra)) will remain active to further engage in the areas of single-cell profiling, organoid research, and data integration.
The in-depth processing and analysis of the single-cell data is ongoing and follows workflows that will allow rapid, seamless deposition and dissemination of raw data and analysis results from HCA|Organoid and beyond. Moreover, HCA|Organoid worked together with the HCA Data Coordination Platform (HCA-DCP) to include and adapt HCA-DCP metadata standards covering organoid data. This ensures long-term sustainability of the outputs from the HCA|Organoid project because data can be deposited using standard organoid workflows even after the project has ended, and those data have long term archival support as part of the HCA-DCP. In addition, the HCA|Organoid Data Portal will serve as an interactive portal for user-friendly access to organoid data. The final version of the HCA|Organoid Data Portal (https://portal.hca-organoid.eu/(si apre in una nuova finestra)) will display the comprehensive single-cell data as soon as initial processing and data mining of the full single-cell sequencing data set is completed. Moreover, the partners of HCA|Organoid are actively contributing to the HCA strategy and coordination and will continue to disseminate HCA|Organoid results as part of the HCA Biological Network “Organoid”. The HCA|Organoid project website (https://hca-organoid.eu(si apre in una nuova finestra)) and the twitter account (https://twitter.com/OrganoidAtlas(si apre in una nuova finestra)) will remain active to further engage in the areas of single-cell profiling, organoid research, and data integration.
The mission of the HCA|Organoid project is to advance biomedical discovery and the development of regenerative therapies by supporting and accelerating disease-centric research in areas such as rare genetic diseases, complex multifactorial diseases and precision oncology. This overarching goal can be achieved by creating an open and inclusive research environment that facilitates collaboration among a broad range of interested researchers, bridging communities and integrating expertise in organoids and single-cell technology.
Beyond the initial focus on colon and brain, the Organoid Cell Atlas shall incorporate datasets from other organoids and organ systems through the HCA data infrastructure and in collaboration with the other HCA Biological Networks.
Therefore, the impact of the HCA|Organoid project occurs on following levels, which together will enhance innovation capacity and foster research on human health issues:
1. Contributing to the HCA and its biomedical vision
The openly available and deeply characterized organoid collection of the HCA|Organoid project will enable functional and disease-centric studies pursuing HCA insights. Thus, providing access to a sufficiently large and well‐characterized collection of normal organoids from healthy individuals provides a reference against which disease‐associated aberrations (e.g. altered gene expression programs or the lack or overrepresentation of certain cell types) can be distinguished from normal population variation. Moreover, the collection of organoids from different individuals with comprehensive single‐cell sequencing and single‐cell imaging data will enable informed decisions to identify the most suitable organoids for disease modeling, drug response profiling, and generation of patient-specific in vitro “avatars” to support personalized treatment decisions.
2. Promoting organoid technology
The pilot action of the HCA|Organoid project did scale organoid production and single‐cell characterization to over two hundred individuals which is a significant step toward driving standardization, providing reference data, and facilitating the adoption of study designs that explicitly account for population variation in organoid research.
3. Connecting communities
The HCA|Organoid project is strongly committed to better connecting the single‐cell and organoid research communities which will boost HCA’s impact on human health. Long-term impact and sustainability will be promoted for example by open sharing of organoids and protocols, the implementation of standard organoid workflows for data integration, long-term archival support as part of the HCA-DCP, and dissemination of results as part of the HCA Biological Network “Organoid”.
Beyond the initial focus on colon and brain, the Organoid Cell Atlas shall incorporate datasets from other organoids and organ systems through the HCA data infrastructure and in collaboration with the other HCA Biological Networks.
Therefore, the impact of the HCA|Organoid project occurs on following levels, which together will enhance innovation capacity and foster research on human health issues:
1. Contributing to the HCA and its biomedical vision
The openly available and deeply characterized organoid collection of the HCA|Organoid project will enable functional and disease-centric studies pursuing HCA insights. Thus, providing access to a sufficiently large and well‐characterized collection of normal organoids from healthy individuals provides a reference against which disease‐associated aberrations (e.g. altered gene expression programs or the lack or overrepresentation of certain cell types) can be distinguished from normal population variation. Moreover, the collection of organoids from different individuals with comprehensive single‐cell sequencing and single‐cell imaging data will enable informed decisions to identify the most suitable organoids for disease modeling, drug response profiling, and generation of patient-specific in vitro “avatars” to support personalized treatment decisions.
2. Promoting organoid technology
The pilot action of the HCA|Organoid project did scale organoid production and single‐cell characterization to over two hundred individuals which is a significant step toward driving standardization, providing reference data, and facilitating the adoption of study designs that explicitly account for population variation in organoid research.
3. Connecting communities
The HCA|Organoid project is strongly committed to better connecting the single‐cell and organoid research communities which will boost HCA’s impact on human health. Long-term impact and sustainability will be promoted for example by open sharing of organoids and protocols, the implementation of standard organoid workflows for data integration, long-term archival support as part of the HCA-DCP, and dissemination of results as part of the HCA Biological Network “Organoid”.