Single-cell transcriptional and epigenomic landscape of human blood immune cells across the lifespan.

T cells underwent the most significant transcriptional remodeling among immune lineages across the human lifespan.

• Single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) were performed on peripheral blood mononuclear cells (PBMCs)
• Donors spanned mid-fetal to late adulthood developmental stages
• Both lymphoid and myeloid lineages showed age-associated reprogramming
• T cells were specifically identified as showing the most significant transcriptional remodeling among all immune lineages examined

ITGB1+CD8+ effector memory T cells played a protective role in young adulthood.

• This cell subset was identified through single-cell transcriptional profiling
• The protective role was specifically associated with the young adulthood stage of the lifespan
• ITGB1 (integrin beta-1) expression characterized this CD8+ effector memory T cell subset
• This finding was part of the broader age-associated T cell reprogramming observations

An immunosuppressive AREG+ natural killer (NK) cell subset was enriched in early childhood.

• This NK cell subset was characterized by high expression of AREG (amphiregulin)
• The subset exhibited low expression of cytotoxic and activating markers
• The subset showed high expression of inhibitory molecules
• Enrichment of this immunosuppressive NK subset was specifically observed during early childhood

Fetal-derived XCL2+CD56bright NK cells showed upregulation of the inhibitory receptor KLRC1.

• This NK cell subset was identified as fetal-derived based on its developmental stage of occurrence
• XCL2 expression and CD56bright phenotype characterized this subset
• KLRC1 (also known as NKG2A) is an inhibitory receptor that was upregulated in this fetal NK subset
• This finding contributes to understanding fetal immune composition and its distinct regulatory mechanisms

IL1Bhi monocytes increased with aging, contributing to inflammaging.

• A monocyte subset characterized by high expression of IL1B (interleukin-1 beta) was identified
• This subset increased in frequency during aging
• The increase in IL1Bhi monocytes was linked to the phenomenon of inflammaging (age-associated chronic low-grade inflammation)
• This finding was identified through single-cell transcriptional profiling of the myeloid lineage across lifespan

The study generated a comprehensive single-cell atlas of peripheral immune cell dynamics across the human lifespan from mid-fetal to late adulthood.

• Both scRNA-seq and scATAC-seq were performed, providing transcriptional and epigenomic data
• PBMCs from healthy donors were sampled across a wide developmental range from mid-fetal to late adulthood
• The atlas encompasses both lymphoid and myeloid lineages
• The dataset reveals various age-related signatures offering insights into immune aging and age-related diseases