Single-Cell Atlas of Human Blood During Healthy Aging

Comprehensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for systematic understanding of human aging. Here, using single-cell RNA/TCR/BCR-seq with protein feature barcoding (20 antibodies), we profiled 317 samples from 166 healthy individuals aged 25 to 85 years old drawn over 3-year period. Dataset spanning ~2 million cells describes 50 subpopulations of blood immune cells, with 14 subpopulations changing with age, including a novel NKG2C+ CD8 Tcm population that decreases with age. We describe age-associated accumulation of Th2 and HLA-DR+ memory CD4 T cells, CCR4+ CD8 Tcm cells and GZMK+ CD8 Tem cells. We validate key findings using 30-plex spectral cytometry panel. We characterize patterns of antigen receptor clonality across subpopulations of T and B cells and describe their age-dependence. Our work provides novel insights into healthy human aging and unique annotated resource of unprecedented depth.

全面、大规模的健康人类血液单细胞分析，针对不同年龄段的样本，是构建系统理解人类衰老框架的关键待办事项之一。本研究采用单细胞RNA/TCR/BCR测序技术，结合蛋白质特征条形码（20种抗体），对166名25至85岁健康个体在三年期间采集的317个样本进行了分析。该数据集覆盖约200万个细胞，描述了50个血液免疫细胞亚群，其中14个亚群随着年龄的增长而变化，包括一种新的NKG2C+ CD8 Tcm细胞亚群，其数量随着年龄的增长而减少。本研究描述了与年龄相关的Th2和HLA-DR+记忆CD4 T细胞、CCR4+ CD8 Tcm细胞以及GZMK+ CD8 Tem细胞的积累。我们利用30-plex光谱流式细胞术检测板验证了关键发现。我们表征了T和B细胞亚群中抗原受体克隆性的模式，并描述了其年龄依赖性。本研究为健康人类衰老提供了新的见解，并构成了一个前所未有的深度注释资源。