Periodic Reporting for period 1 - 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) Reporting period: 2020-01-01 to 2020-12-31 Summary of the context and overall objectives of the project The HCA|Organoid is a European research project that will establish 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 will complement 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 will initially focus on establishing single-cell profiles of human organoids and matched primary tissue from healthy donors. The project will derive and comprehensively characterize human brain and colon organoids from 100 individuals each. This resource will enable future discovery-driven and translational research on rare genetic diseases, complex multifactorial diseases, and on cancer. The value of the “Organoid Cell Atlas” for disease‐centric research will be demonstrated through proof-of-concept studies. Moreover, a multi‐tissue human organoid platform comprising a “living biobank” and a HCA|Organoid Data Portal for data sharing and user‐friendly analysis will be established. Consequently, the results obtained by the HCA|Organoid project will 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. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far "In order to lay the foundations of the first ""Organoid Cell Atlas"" the HCA|Organoid research team follows a clear project structure that streamlines all activities to focus on i) establishment of a sharable organoid resource for colon and brain organoids, ii) generation of single-cell sequencing datasets, iii) generation of single-cell imaging datasets, iv) integrative data analysis, v) integration into the global HCA infrastructure, vi) performance of disease pilot studies to demonstrate the value of the organoid platform, and vii) project and innovation management to ensure effective, impactful, and sustainable project progression. The Covid-19 pandemic outbreak did affect the HCA|Organoid project by mainly limiting sample acquisition from hospitals and cell banks which are essential for the derivation of colon and brain organoids, respectively. Consequently, the limited generation of organoid samples affected all downstream activities in the HCA|Organoid project. Nevertheless, the HCA|Organoid research team successfully established the workflows for colon and brain organoid derivation to allow generation and biobanking of the first organoids for profiling. Moreover, the protocols and workflows for single-cell profiling were optimized to allow efficient sample preparations, sequencing, and high-throughput imaging analysis. The progress on disease pilot studies, data analysis, and integration into the HCA infrastructure was mainly conceptual due to lack of sufficient single-cell data from colon and brain organoids. Significant progress was made on project management and dissemination activities. The first HCA|Organoid project meeting was organized, and virtual attendance allowed efficient information exchange between all project partners. Noteworthy is the public release of the HCA|Organoid project website (https://hca-organoid.eu) the implementation of a twitter account (https://twitter.com/OrganoidAtlas) and the publication of a strategy paper which describes the vision and the anticipated impact of the Organoid Cell Atlas (https://doi.org/10.1038/s41587-020-00762-x)." Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) 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.The impact of the HCA|Organoid project will be on following levels, which together will enhance innovation capacity and foster research on human health issues:1. Contributing to the HCA and its biomedical visionThe 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, a 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 technologyThe pilot action of the HCA|Organoid project will scale organoid production and single‐cell characterization to over two hundred individuals which will drive standardization, provide reference data, and facilitate the adoption of study designs that explicitly account for population variation in organoid research.3. Connecting communitiesThe 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, training, and outreach activities. Logo
