European pilot actions to build the foundations of the human cell atlas

The Human Cell Atlas initiative (HCA) aims to create molecular reference maps of all human cells to pool and expand knowledge of the diverse cells found within the human body in order to better understand human health, but also to improve diagnosis, monitoring and treatment of diseases.

As a contribution to this global initiative, The European Commission is funding six pilot actions within the Horizon2020 Research and Innovation Framework Programme, starting from January 2020. Each of those projects has been designed to characterize single cells or their nuclear components, their interactions and/or spatial location in tissues from one human organ, using state-of-the-art singe cell technologies, analytical methods and computational tools, and brings together European experts in the respective fields who are joining their efforts to support the creation of the human cell atlas:

The project BRAINTIME aims to increase our understanding of the developing and the ageing human brain. Based on multi-omic analysis of the developing human midbrain and hindbrain, the group will generate an atlas of key monoaminergic cell populations, embed the new cell type maps in 3D contexts and temporal developmental models and set up a technological and analytical pipeline for the analysis of brain tissue at the single-cell level that can be used by the research community.

The DISCOVAIR consortium focuses on the lung. Combining multimodal molecular profiling of lung tissue cells with a detailed spatial mapping of the identified cell states, 3D reconstruction of lung tissue architecture, and in-depth molecular phenotyping of local cellular neighbourhoods, the group will generate detailed knowledge of the cells of the lung, their fixed and variable molecular features, their interactions and their organization into macroscopic tissue architecture in health and disease.

ESPACE aims to map the human pancreas, integrating molecular profiles, including transcriptome and epigenomics data from more than 1 million single cells, with tissue proteomics to address fundamental questions of cell state and phenotype in healthy adults and during foetal development.

The HCA Organoid initiative will establish a “Human Organoid Atlas” within the HCA, initially focusing on two organs (colon and brain) but adding other organs as pilot studies. The project will establish single-cell transcriptomes, single-cell epigenomes, and time-series imaging for several thousand organoids and matched primary tissue to quantify normal population variation and provide a baseline for disease studies.

The project HUGODECA works on understanding the cellular composition and organization of the developing human gonads. The analytical concept is grounded on the integration of multiple synergistic expertise and technologies including single cell profiling, spatial transcriptomics, 2D mass cytometry, as well as cyclic immunofluorescence and 3D imaging of optically cleared gonads.

The HUTER project will provide unprecedented insight at transcriptomic, genomic and spatial changes of the uterus throughout the menstrual cycle as well as across lifespan.

This joint website will provide you with an overview of the six projects, contacts to reach out to if you want to learn more about an individual project, and display joint cluster activities. Websites of the individual projects will be added as they become available. The findings from the projects will later be integrated and made available through the HCA Data Coordination Platform.

Molecular atlas of the brain across the human lifespan

BRAINTIME brings together six laboratories that are international leaders in the field of single-cell genomics with the aim to apply their knowledge and expertise to understand the human brain. In BRAINTIME, we will:

(1) Perform a comprehensive multi-omic analysis of the developing human midbrain and hindbrain to generate an atlas of key monoaminergic cell populations in healthy adulthood, ageing and neurodegenerative disease;

(2) Embed our new cell type maps into 3D contexts and temporal developmental models by integrating new approaches for computational modelling, cell fate tracking, spatial analysis and capturing cell-cell interactions;

(3) Establish single-cell genomics-empowered ex-vivo protocols and standardized ex-vivo/in-vivo projection algorithms to allow flexible model testing and perturbation analysis on midbrain and hindbrain tissues;

(4) Establish an effective and sustainable technological and analytical pipeline for the analysis of brain tissue at the single-cell level that can be used by the community to probe other brain regions or states and be extended to other human tissues.

Achieving these objectives will significantly advance the Human Cell Atlas initiative by contributing major new datasets on human brain development and ageing, and ensure a key role for European labs in the global effort. The US partner (Ed Lein / Allen Institute) ensures a crucial connection to the NIH BRAIN initiative, including access to significant computational and atlasing resources. Through the SME partner (CartaNA), we gain access to cutting edge in-situ sequencing methods and support the fledgling European biotech industry in the single-cell field.

Coordinator: Sten Linnarsson (Karolinska Institutet/ Sweden)

Contact: sten.linnarsson@ki.se and anna.johnsson@ki.se

Discovering the cellular landscape of the airways and the lung

Lung diseases are a leading cause of death, with increasing incidence and lack of curative interventions. The development of novel therapeutic interventions is hampered by our incomplete knowledge of the cellular complexity of the lung, as evidenced by the recent identification of the CFTR-expressing ionocyte. To overcome this limitation, we urgently need to acquire detailed knowledge of the cells of the lung, their fixed and variable molecular features, their interactions and their organization into macroscopic tissue architecture in health and disease. To achieve this, discovAIR aims to establish the first draft of the Human Lung Cell Atlas. Herein, discovAIR will combine multimodal molecular profiling of lung tissue cells with a detailed spatial mapping of the identified cell states, 3D reconstruction of lung tissue architecture, and in-depth molecular phenotyping of local cellular neighbourhoods. We will develop novel computational approaches to integrate the multilevel data of the spatial and the cellular branches of discovAIR. To identify the molecular phenotypes of cells in disease, discovAIR will include lung tissue from patients with asthma, COPD and IPF in the molecular profiling and spatial mapping effort.

Moreover, discovAIR will chart cell state transitions from health to disease in a novel experimental approach, the lung cell perturbation map. The discovAIR results will be shared with the basic, translational and clinical scientific community as well as diagnostic and pharmaceutical industry through an open-access data visualization and exploration platform. For sustainability, this platform will be embedded in the Human Cell Atlas infrastructure. The discovAIR results will facilitate progress in regenerative and precision medicine and identify novel candidates for precision diagnostics and curative interventions in lung disease, thereby contributing to healthy ageing and active living in Europe.

Coordinator: Dr. Martijn C. Nawijn (Academisch Ziekenhuis Groningen/ The Netherlands)

Contact: info-discovair@humancellatlas.org

Website: https://discovair.europescience.eu/

Twitter: @discovAIR_HCA

Human Cell Atlas of the Pancreas

The human pancreas is a physiologically unique organ involved in the secretion of several hormones, such as insulin, thus regulating blood sugar levels, as well as the secretion of enzymes for the digestive system. Several human diseases are associated with the pancreas: Pancreatic andenocarcinoma is one of the most aggressive cancers in humans and pancreatitis is a common potentially life-threatening disorder related to adverse lifestyle conditions. A very common chronical disease affecting the pancreas is Diabetes mellitus, a metabolic disorder that is characterised by high blood sugar levels due to the lack of insulin produced in the pancreas. Despite its high physiological importance, its high autolytic activity makes the pancreas a challenging tissue to study.

ESPACE has been formed as a merger of three prior Human Cell Atlas (HCA) early pilot studies of the pancreas funded by the Chan Zuckerberg initiative. Based on methods and standards for sample procurement, single cell profiling, spatial proteomics, and computational pipelines developed in those early pilots, ESPACE will now build a first version of the Human Cell Atlas of the Pancreas. The group will integrate molecular profiles, including transcriptome and epigenomics data from more than 1 million single cells, with tissue proteomics allowing to address fundamental questions of cell state and phenotype in healthy adults and during foetal development. Thus, the project will provide a first version of an open single cell repository of the pancreas built upon the Data Coordination Platform of the HCA. Exploring the benefit of the HCA of the pancreas for tackling pancreatic diseases,

ESPACE will reach out into types 2 diabetes. Besides creating a unique and first-of-its-kind comprehensive atlas of the human pancreas the methods and standards developed by ESPACE will be of high relevance for HCA projects in other organs.

Coordinator: Prof. Dr. Roland Eils (Charité – Universitätsmedizin Berlin/ Berlin Institute of Health, Germany)

Contact: info@linq-management.com

Website: https://www.espace-h2020.eu/

Twitter: @HiDiHlabs

Hashtag: #espaceH2020

HCA|Organoid is a 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.

The Human Cell Atlas (HCA) is descriptive by definition, as it seeks to map all cells in the human body. Yet its goal of “understanding fundamental human biological processes and diagnosing, monitoring, and treating disease” (HCA Whitepaper) depends on our ability to draw functional/causal/mechanistic conclusions relevant to human diseases. Personalized organoid technology aptly fills this gap, as it makes human tissue amenable to functional studies and faithful disease modeling in vitro.

This project will firmly establish a "Human Organoid Atlas" within the HCA. Initially focusing on two organs (colon and brain: 100 persons each) additional organs will be included as pilot studies with organoids derived from up to 20 individuals in total. It is, for example, envisioned that pancreas organoids will be included in collaboration with Human Cell Atlas affiliated projects that focus on the single-cell dissection of the human pancreas. We will establish single-cell transcriptomes, single-cell epigenomes, and time-series imaging for several thousand organoids and matched primary tissue. This resource will quantify normal population variation and provide a baseline for disease studies. We will show its practical utility by proof-of-concept disease modeling for genetic epilepsy (brain) and large-scale characterization of disease-linked genetic variants (colon).

Anticipated impact: 1. Deeply characterized organoid collection enables functional and disease-centric studies pursuing HCA insights. 2. Single-cell dataset provides reference of population variation under highly standardized conditions. 3. Linking single-cell profiling and organoids will boost HCA’s impact on human health.

Coordinator: Dr. Christoph Bock (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria)

Contact: cbock@cemm.oeaw.ac.at

Webpage:  https://www.hca-organoid.eu/

Twitter: @OrganoidAtlas

Hashtag: #HCAOrganoid or #OrganoidCellAtlas

Human Gonad Developmental Cell Atlas

The single ground-breaking goal of the HUGODECA project is to describe the cellular composition and organization of the developing human gonads and to understand how they change during sex determination into testes in males and ovaries in females. What are the underlying mechanisms and first molecular and cellular events that accompany the differentiation and divergence of embryonic gonads? How and when do male and female cell lineages diverge and specific traits emerge? HUGODECA focuses on healthy gonad development, but our reference model will be tested using specific ex vivo assays mimicking Differences/Disorders of Sex Development (DSD).

To reach this ambitious goal, the HUGODECA consortium brings together leading European academic and industrial experts from 5 different EU countries. It includes active contributors and executives of the Human Cell Atlas (HCA) which will ensure complementarity with other ongoing HCA efforts.

The overall HUGODECA concept is grounded on the integration of multiple synergistic expertise and technologies: Single cell profiling, Spatial transcriptomics, 2D Mass cytometry and cyclic immunofluorescence and 3D imaging of optically cleared gonads. HUGODECA will implement novel tools, analytical and computational methods to process and integrate multidimensional OMICS and image data across different platforms. It will evaluate the accuracy of ex vivo culture models of human gonadal development and assess consequences of altering key signaling pathways.

HUGODECA will build the first multiscale developmental cell atlas and unprecedented reference maps of male and female human gonads. It will implement an interactive and multi-dimensional online portal for clinicians, scientists and the public including DSD patient associations. HUGODECA shall improve our understanding of DSD, which is a major pediatric concern, requiring complex and highly specialized medical treatment and psychosocial care.

Coordinator: Dr. Alain Chedotal (Institut National de la Sante et de la Recherche Medicale/ France)

Webpage:  https://hugodeca-project.eu/

Twitter: @Hugodecaproject

Human Uterus Cell Atlas

The Human Uterus Cell Atlas (HUTER) project aims to create the single-cell and spatial reference map of the human uterus. HUTER project will provide unprecedented insight at transcriptomic, genomic and spatial changes of this important female organ not only throughout the menstrual cycle but also across lifespan.

The human uterus is a flagship reproductive organ with profound implications not only in reproduction but also in women´s health. HUTER can advance the Human Cell Atlas initiative for the exploitation potential in Obstetrics and Gynaecology and biomedicine research areas such as Regenerative Medicine or Reproductive Medicine. The uterus is itself a model for regenerative medicine since (i) endometrial tissue regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types, and (ii) myometrial tissue has remarkable regenerative capacity and undergoes extensive remodelling throughout pregnancy.

Hence, the primary motivation of HUTER stems from the need to better understand the human uterus in order to more effectively address uterine diseases that impact women´s health such as myomas or endometriosis and/or might contribute to infertility, infant and maternal mortality and morbidity. The HUTER technological and biological platform will be a crucial resource for the scientific and clinical communities to define the cellular basis of health and disease, allowing the rapid development of new diagnosis and prognosis tools and therapeutic advancements in the field.

Coordinator: Dr. Carlos Simón (INCLIVA, Spain)

Contact: contact@huter-hca.eu

Webpage: https://huter-hca.eu/

Twitter: @Huter_HCA

Instagram: huter_hca


These projects have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement numbers 874606, 874656, 874710, 874741, 874769, 874867.