Gene

Rejuvenation

Cell biology

Parabiosis

Haematopoiesis

Heterochrony

Biology

Stem cell

Immunology

Hematopoietic stem cell

Genetics

Transcriptome

Progenitor cell

Lymphopoiesis

Stem cell theory of aging

Ontogeny

Gene expression

Stem cell factor

Cell stem cell

<h2>Summary</h2> 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.

Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues