Mangiola S, Milton M, Ranathunga N, Li-Wai-Suen Csn, Odainic A, Yang E, Hutchison W, Garnham A, Iskander J, Pal B, Yadav V, Rossello Jfj, Carey V J, Morgan M, Bedoui S, Kallies A, Papenfuss A T
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
bioRxiv. 2024 Apr 29:2023.06.08.542671. doi: 10.1101/2023.06.08.542671.
Understanding tissue biology's heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system. We used this resource and a novel multilevel modelling approach to track immune ageing and test differences across sex and ethnicity. We uncovered conserved and tissue-specific immune-ageing programs, resolved sex-dependent differential ageing and identified ethnic diversity in clinically critical immune checkpoints. This study provides a quantitative baseline of the immune system, facilitating advances in precision medicine. By sharing our immune map, we hope to catalyse further breakthroughs in cancer, infectious disease, immunology and precision medicine.
了解组织生物学的异质性对于推进精准医学至关重要。尽管免疫系统在组织稳态中处于核心地位，但人类组织和人口统计学中免疫细胞分布及相互作用的详细而全面的图谱仍然难以捉摸。为填补这一空白，我们整合了来自12981个单细胞RNA测序样本的数据，并整理了来自45个解剖部位的2900万个细胞，以创建健康免疫系统的全面组成和转录健康图谱。我们利用这一资源和一种新颖的多层次建模方法来追踪免疫衰老，并测试性别和种族之间的差异。我们发现了保守的和组织特异性的免疫衰老程序，解决了性别依赖性差异衰老问题，并确定了临床关键免疫检查点中的种族多样性。这项研究提供了免疫系统的定量基线，促进了精准医学的发展。通过分享我们的免疫图谱，我们希望催化癌症、传染病、免疫学和精准医学领域的进一步突破。
