Absolute scaling of single-cell transcriptomes identifies pervasive hypertranscription in adult stem and progenitor cells

Abstract

Hypertranscription supports biosynthetically demanding cellular states through global transcriptome upregulation. Despite its potential widespread relevance, documented examples of hypertranscription remain few and limited to early development. Here, we demonstrate that absolute scaling of single-cell RNA-sequencing data enables the estimation of total transcript abundances per cell. We validate absolute scaling in known cases of developmental hypertranscription and apply it to adult cell types, revealing a remarkable dynamic range in transcriptional output. In adult organs, hypertranscription marks activated stem/progenitor cells with multilineage potential and is redeployed in conditions of tissue injury, where it precedes bursts of proliferation during regeneration. Our analyses identify a common set of molecular pathways associated with both adult and embryonic hypertranscription, including chromatin remodeling, DNA repair, ribosome biogenesis, and translation. These shared features across diverse cell contexts support hypertranscription as a general and dynamic cellular program that is pervasively employed during development, organ maintenance, and regeneration.