The young circulatory milieu capable of delaying aging in individual tissues is of interest as rejuvenation strategies, but how it achieves cellular- and systemic-level effects has remained unclear. Here, we constructed a single-cell transcriptomic atlas across aged tissues/organs and their rejuvenation in heterochronic parabiosis (HP), a classical model to study systemic aging. In general, HP rejuvenated adult stem cells and their niches across tissues. In particular, we identified hematopoietic stem and progenitor cells (HSPCs) as one of the most responsive cell types to young blood exposure, from which a continuum of cell state changes across the hematopoietic and immune system emanated, through the restoration of a youthful transcriptional regulatory program and cytokine-mediated cell-cell communications in HSPCs. Moreover, the reintroduction of the identified rejuvenating factors alleviated age-associated lymphopoiesis decline. Overall, we provide comprehensive frameworks to explore aging and rejuvenating trajectories at single-cell resolution and revealed cellular and molecular programs that instruct systemic revitalization by blood-borne factors.

能够在单个组织中延缓衰老的年轻循环环境作为恢复活力的策略是令人感兴趣的，但它如何实现细胞和全身水平的效果仍不清楚。在这里，我们构建了一个跨衰老组织/器官的单细胞转录组图谱及其在异慢性联体共生 (HP) 中的复兴，这是研究系统性衰老的经典模型。一般来说，HP 可以使成体干细胞及其组织中的生态位恢复活力。特别是，我们将造血干细胞和祖细胞 (HSPC) 确定为对年轻血液暴露最敏感的细胞类型之一，通过恢复年轻的转录调控，造血和免疫系统的细胞状态连续变化。 HSPCs 中的程序和细胞因子介导的细胞间通讯。而且，重新引入已确定的再生因子缓解了与年龄相关的淋巴细胞生成下降。总体而言，我们提供了全面的框架来探索单细胞分辨率下的衰老和恢复活力轨迹，并揭示了通过血源性因子指导全身再生的细胞和分子程序。