Absolute proliferation and death rates in tissues revealed by single-cell transcriptomics

Whether a tissue expands, maintains, or declines is determined by the balance of cell proliferation and death rates, yet no existing method can measure both rates in vivo — a blind spot at the center of cancer biology, aging, and immunotherapy. Here we show that absolute proliferation and death rates can be quantified from a standard single-cell RNAseq snapshot using tissue dynamics inference (TIDYI), a method we develop and validate experimentally across tissue systems. Applying TIDYI to published datasets reveals that tumor growth slowdown during cancer progression is driven primarily by increased cell death rather than decreased proliferation, that skin progenitor loss during aging results from increased death rather than reduced proliferation, and that tumor-infiltrating immune cells turn over with a half-life of ~15 hours. TIDYI expands single-cell transcriptomics from characterizing cellular states to quantifying the rates that determine tissue fate, without need for longitudinal sampling, genetic engineering or exogenous labels.