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bioRxiv · 10.64898/2026.09.11.750312

A lifespan-scale single-cell atlas defines an early-childhood immunometabolic transition linked to age-referenced immune states

Zheng, J.·Shi, Y.·Sun, Y.·Wang, Y.·Li, R.·Wang, P.·Chang, S.·Pan, L.·Tan, H.·Yue, T.·Qu, K.·Zheng, X.·Guo, C.·Weng, J.
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Abstract

Childhood represents a critical period with rapid metabolic and immune remodeling, during which perturbations may have lasting consequences for health. We integrated single-cell RNA sequencing (scRNA-seq) profiles of peripheral blood mononuclear cells (PBMCs) from 2,008 healthy individuals aged 0-100 years. Age-resolved modeling highlighted an early-childhood transition centered at age 6, characterized by coordinated remodeling of metabolism-related transcriptional programs, particularly in monocyte and B-lineage cells. Matched serum metabolomics and lipidomics in a pediatric subcohort detected a temporally concordant wave of metabolite and lipid changes around ages 6-8 and extensive metabolite/lipid-transcript associations, prominently involving steroid and phospholipid species. Building on these findings, we developed an immunometabolic transition score and age-specific reference chart, which were evaluated in an independent healthy cohort and applied to quantify deviations in pediatric immune disorders. These findings highlight a coordinated immunometabolic transition in early childhood and provide an age-referenced framework for distinguishing atypical immune-state variation from healthy age-associated variation.

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Zheng, J., Shi, Y., Sun, Y., Wang, Y., Li, R., Wang, P., Chang, S., Pan, L., Tan, H., Yue, T., Qu, K., Zheng, X., Guo, C., Weng, J.. 2026-09-18. A lifespan-scale single-cell atlas defines an early-childhood immunometabolic transition linked to age-referenced immune states. https://doi.org/10.64898/2026.09.11.750312

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