SCIENTISTS ASSEMBLE WORLD’S FIRST IMMUNE CELL ATLAS FROM DIVERSE ASIAN POPULATIONS

SINGAPORE – Researchers from the A*STAR Genome Institute of Singapore (A*STAR GIS), together with collaborators from South Korea, Japan, Thailand, and India, have assembled the world’s first Asian Immune Diversity Atlas (AIDA)—a multi-national survey of human blood at single-cell resolution. The landmark study, published in the scientific journal Cell in March 2025, has the potential to advance Precision Medicine and empower the development of next-generation diagnostics and therapeutics tailored specifically for Asian populations.

The study of human immune cells provides critical insights into diagnosing, understanding, and treating infectious diseases, autoimmune disorders, and blood cancers. Clinically, immune cell proportions are already used to diagnose conditions like tuberculosis and leukaemia. Recent technological advances in single-cell genomics now allow researchers to analyse individual cells in unprecedented detail, enabling more precise diagnostics and targeted treatments—for example, distinguishing immune signatures associated with lupus or predicting responses of cancers to immunotherapy.

However, diagnostic approaches developed using data from one population, such as Europeans, often do not accurately translate to other populations, for example Asians. Healthy immune baselines and disease risk factors can vary widely due to differences in age, sex, genetics, lifestyle, and environment. Historically, biomedical research has largely focused on European populations, underscoring the importance of creating tailored diagnostic criteria based on data from Asian populations.

Profiling Asia’s Immune Diversity at Single-Cell Resolution

To address this gap, the A*STAR GIS-led AIDA consortium profiled the healthy immune systems of diverse Asian populations. Using advanced single-cell genomics methods, the researchers analysed over 1.2 million immune cells from blood samples of 625 healthy donors across five Asian countries. AIDA is a flagship project of the Asia network of the international Human Cell Atlas (HCA) consortium, which aims to create comprehensive reference maps of human cells to enhance disease diagnosis, monitoring, and treatment.

The AIDA team^[1] established healthy immune reference ranges for multiple Asian population groups, including Singaporean Chinese, Malay, and Indian ethnicities. They assessed how factors like ethnicity, age, and sex influenced immune cell proportions and gene expression. The results revealed that self-reported ethnicity contributes nearly as much as sex to variation in blood cell proportions, with significant differences also observed across ethnicities in age-related and sex-related cellular changes. Additionally, certain cell states and gene products showed 2- to 8-fold higher abundance in specific populations, providing insights which may help refine biomarkers for diagnosing diseases and predicting disease risks.

Further, the researchers identified molecular properties potentially unique to Asian populations, which could help us understand genetic causes of infectious and autoimmune diseases, as well as differences in disease susceptibility. The AIDA resource, available on the Chan Zuckerberg Cell by Gene website and the HCA Data Portal, offers a powerful reference for developing tailored diagnostic and therapeutic strategies better suited to Asian patients.

A Landmark Collaboration for Precision Health in Asia

The collaborative nature and significance of the AIDA project reflect the urgent need to expand biomedical research beyond traditionally studied populations.

Dr Shyam Prabhakar, Associate Director at A*STAR GIS and senior author of the study, shared, “In the next phase of research, we are scaling up the AIDA resource, and extending our single-cell genomics analysis to Asian patients, including those in Singapore. We foresee that AIDA will empower the development of Precision Medicine efforts in Singapore, Asia, and beyond.”

Dr Jay Shin, Senior Group Leader at A*STAR GIS, Team Leader at RIKEN, Japan, and senior author of the study, said, “The AIDA resource is the fruit of a hugely enjoyable and collegial collaboration across the Human Cell Atlas Asia network, through which we brought together investigators from across Asia to lead and engage in world-leading research.”

Dr Park Woong-Yang, Director of Samsung Genome Institute, Samsung Medical Center in South Korea and senior author of the study, said, “Historically, most studies have focused on populations of European ancestries, and biomedical properties are less well-understood for non-European donors. We have demonstrated the importance of including diverse populations in biomedical research.”

Dr Alexandra-Chloé Villani, Institute Member of the Broad Institute, Assistant Professor at Massachusetts General Hospital and Harvard Medical School, and author of the study, said, "This is a pivotal step towards the Human Cell Atlas mission of creating a comprehensive reference map of human cells to transform our understanding of health and disease and to drive major advances in healthcare and medicine worldwide. This groundbreaking study paves the way for the future development of diagnostics and therapies tailored to individual populations."

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About A*STAR’s Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS pursues the integration of technology, genetics, and biology towards academic, economic and societal impact, with a mission to "read, reveal and (ω)rite DNA for a better Singapore and world".

Key research areas at the GIS include Precision Medicine & Population Genomics, Genome Informatics, Spatial & Single Cell Systems, Epigenetic & Epitranscriptomic Regulation, Genome Architecture & Design, and Sequencing Platforms. The genomics infrastructure at the GIS is also utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit www.a-star.edu.sg/gis.

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About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

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ANNEX A: Additional quotes
Dr Kock Kian Hong, Scientist at A*STAR GIS and first author of the study, said, “We were able to examine cells and genes, including those known to be relevant to disease risk, pathogenesis, and diagnostics, at an unprecedented resolution and scale, given the single-cell genomics approaches employed by our AIDA consortium.”

Dr Patrick Tan, Executive Director of Precision Health Research, Singapore (PRECISE), Senior Vice Dean (Research) at Duke-NUS Medical School, and Chief Scientific Officer at A*STAR GIS, said, “This effort from scientists from Singapore, South Korea, Japan, Thailand, and India establishes a paradigm for large-scale single-cell genomics projects at the regional and global scale, with the potential to transform diagnostics for patients across Asia.”

Dr Norbert Tavares, Senior Science Program Manager for Cell Science at the Chan Zuckerberg Initiative, said, “The data generated by AIDA will contribute to a robust and unique collection of single-cell datasets to the HCA and available on Chan Zuckerberg Cell by Gene. The insights derived from this project will benefit researchers around the world and make progress toward understanding health and disease.”

ANNEX B: Examples of immune differences found across Asian populations in the AIDA study

1. Monocyte proportion differences across countries (Thailand) and its implications for diagnostics
2. Treg cell depletion in Korean donors (South Korea) and its implications for autoimmune diseases
3. Interaction between self-reported ethnicity and age (Singaporean Chinese, Singaporean Malay, Korean) and its implications for autoimmune diseases
4. Differential expression of disease-associated genes (Singaporean Chinese, Singaporean Malay, Singaporean Indian), and pinpointing possible disease mechanisms
5. Intersection with prior disease studies involving Japanese cohorts, and pinpointing possible disease mechanisms

1. Monocyte proportion differences across countries (Thailand) and its implications for diagnostics

   The proportions of immune cells in blood can serve as diagnostic markers for diseases, such as the ratio of monocytes to lymphocytes (active tuberculosis), relative monocyte proportion (leukaemia), and lymphocyte abundance (lupus). We found that monocyte proportions were lower on average in our Thai donors. Our findings suggest that it is important to consider self-reported ethnicity in determining diagnostic baselines.
   

2. Treg cell depletion in Korean donors (South Korea) and its implications for autoimmune diseases

   We found much lower regulatory T (Treg) cell proportions in our Korean donors, which is a cell type that has been implicated in autoimmune diseases. Our findings may be helpful for understanding differences in disease susceptibility across populations, and can motivate further studies of autoimmune disease prevalence across populations. There have been a few prior studies that examined differences in disease prevalence across populations. For example, a study focused on Manhattan, New York, USA, found that the prevalence of lupus was higher among Asian women than white women. The combined analysis of detailed immune phenotypes with studies of disease prevalence across diverse populations can help us better understand and treat diseases.
   

3. Interaction between self-reported ethnicity and age (Singaporean Chinese, Singaporean Malay, Korean) and its implications for autoimmune diseases

   Reduced levels of the CD4⁺ T naïve cell subtype have been reported in hepatitis C virus-infected patients and lupus patients, and may serve as a possible diagnostic marker. We find that this cell subtype can vary in levels depending on a donor’s self-reported ethnicity and age. For example, our Korean, Singaporean Chinese, and Singaporean Malay donors showed differences in the trends of this cell subtype with increasing age. Both self-reported ethnicity and age need to be considered in deploying CD4⁺ T naïve cell levels as a diagnostic marker.
   

4. Differential expression of disease-associated genes (Singaporean Chinese, Singaporean Malay, Singaporean Indian), and pinpointing possible disease mechanisms
   

   FCER1A is a gene that has been implicated in the risk of allergic disease, and we find that the expression of this gene differs between Singaporean Chinese and Singaporean Indian donors. This gene expression pattern may be due to differences in the prevalence of a genetic variant, which is more frequent in Indian donors than Chinese donors. Our findings can highlight genes of interest for investigating differences in disease risk and susceptibility across populations.
   

5. Intersection with prior disease studies involving Japanese cohorts, and pinpointing possible disease mechanisms

Prior studies of human populations, including Japanese cohorts, have nominated regions within our genome that may underlie disease. For example, the “rs2230500” genetic variant has been implicated in rheumatoid arthritis, including in Japanese donors. This variant is common in East Asians, but rare in non-Asian populations. Our Asian Immune Diversity Atlas allows us to suggest links between this genetic variant and specific cell types and genes, such as the hypoxia gene HIF1A, and a B cell subtype involved in the body’s immune response to pathogens. Our findings allow us to better understand diseases and develop strategies for disease therapies that target certain genes and cell types.