January 31, 2025
Bulletin interne de l'Institut Pasteur
Human Cell Atlas project: spectacular progress to accelerate medical research and improve understanding of the human body
Detailed characterization of human cells in all states – whether healthy, sick, developing or adult – represents a major challenge for biology. The Human Cell Atlas (HCA) consortium (Rood et al., 2024), launched in 2016, has made remarkable progress in this field. This international scientific project, which aims to produce a comprehensive map of all the cells in the human body, recently reached a key milestone with the publication of a collection of more than 40 articles in Nature and other Nature Portfolio journals. The articles shed light on the genetic map of developing tissues and organs in adults and the development of revolutionary new analytical methods involving artificial intelligence and machine learning – like SCimilarity, which is revolutionizing the analysis of single cell technologies and speeding up large-scale cell classification and annotation.
This research demonstrates the potential of experimental and computational approaches in single cell and spatial genomics to reveal fundamental mechanisms governing health and human disease. Key discoveries include placenta formation, skeletal and skin development, lung responses to COVID-19, novel cell states in the gut and vascular system, and the impact of genetic variations on disease. By mapping more than 100 million human cells from 10,000 donors, this research illustrates the HCA's ambition to capture all of human diversity – whether ethnic, genetic, geographical, or age- or sex-related.
Institut Pasteur scientist Dr. Clarisse Ganier has been playing an active role in the Human Cell Atlas since 2019. She has contributed to this collective effort by publishing several articles in collaboration with the consortium that demonstrate major progress in our understanding of developing skin cells (Gopee et al., 2024) (Morioka et al., in press), anatomical differences in adult skin and skin cancer patients (Ganier et al., 2024), as well as the use of data analysis to predict cell localization in a tissue section (Ganier, 2024). She is very keen to maintain her involvement in this vast project as she works in Professor Yasmine Belkaid's laboratory, where she is planning to establish an atlas of skin cells during pregnancy. She is particularly interested in how immune cells react to the major hormonal and physiological changes that occur in pregnancy. In anticipation of this project, close collaboration is being developed with various core facilities at the Institut Pasteur, including the Single Cell Biomarkers UTechS led by Milena Hassan, the Biomics Platform led by Marc Monot, and the Histology Platform led by David Hardy.
Caption: In situ sequencing (pre-Xenium, 10X genomics) of around 200 genes of interest in a skin section, revealing the different structures of human facial skin, including hair follicles and sebaceous glands.
Clarisse Ganier emphasizes the "transformative impact of this project on our understanding of the human body." The initiative, which has been described as a "Google Maps" for cell biology, is establishing a key source of information and data for detecting and analyzing changes underpinning health and disease. These collective efforts will also pave the way for more precise diagnoses, drug discovery and advances in regenerative medicine.
The HCA also reflects a vision for fairer science by promoting open data sharing between scientists worldwide. In making these valuable resources available to everyone, the HCA is helping to reduce disparities in research and strengthen global collaboration. The HCA consortium is independent and is led by scientists, with an Organizing Committee composed of 35 members from 14 countries, co-chaired by Sarah Teichmann (UK) and Aviv Regev (USA). The project is supported by funding from various sources including Inserm, CIFAR, the Chan Zuckerberg Initiative, the Wellcome Trust and many others.
The Human Cell Atlas represents a bold, collaborative vision of contemporary science, rooted in the collective interest and offering promising prospects for transforming biomedical research and improving the lives of millions of people worldwide.
Links to shared datasets in the publications mentioned:
https://spatial-skin-atlas.cellgeni.sanger.ac.uk/
https://developmental.cellatlas.io/fetal-immune
References
• Ganier, C. (2024). Unlocking skin’s symphony: Single-cell and spatial transcriptomics reveal the harmonious interplay among diverse cell populations. The Journal of Investigative Dermatology, 144(9), 1917–1920.
• Ganier, C., Mazin, P., Herrera-Oropeza, G., Du-Harpur, X., Blakeley, M., Gabriel, J., Predeus, A. V., Cakir, B., Prete, M., Harun, N., Darrigrand, J.-F., Haiser, A., Wyles, S., Shaw, T., Teichmann, S. A., Haniffa, M., Watt, F. M., & Lynch, M. D. (2024). Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 121(2), e2313326120.
• Gopee, N. H., Winheim, E., Olabi, B., Admane, C., Foster, A. R., Huang, N., Botting, R. A., Torabi, F., Sumanaweera, D., Le, A. P., Kim, J., Verger, L., Stephenson, E., Adão, D., Ganier, C., Gim, K. Y., Serdy, S. A., Deakin, C., Goh, I., … Haniffa, M. (2024). A prenatal skin atlas reveals immune regulation of human skin morphogenesis. Nature, 1–11.
• Rood, J. E., Wynne, S., Robson, L., Hupalowska, A., Randell, J., Teichmann, S. A., & Regev, A. (2024). The Human Cell Atlas from a cell census to a unified foundation model. Nature.
• Morioka N., Ganier C*., Watt M. F*. Fetal fibroblast heterogeneity defines dermal architecture during human embryonic skin development. J. Invest. Dermatol. In press.