Our findings introduce an approach towards maximizing single-cell RNA-seq profiling. Our analyses reveal a common set of molecular pathways associated with hypertranscription across adult organs, including chromatin remodeling, DNA repair, ribosome biogenesis and translation. In addition to the association between hypertranscription and the stem/progenitor cell state, we dissect the relationship between transcriptional output and cell cycle, ploidy and secretory behavior. Hypertranscription marks cells with multilineage potential in adult organs, is redeployed in conditions of tissue injury, and can precede by 1-2 days bursts of proliferation during regeneration. We find that many different multipotent stem and progenitor cell populations are in a state of hypertranscription, including in the hematopoietic system, intestine and skin. The results reveal a remarkable dynamic range in transcriptional output among adult cell types. Absolute scaling enables an estimation of total transcript abundances per cell, which we validate in embryonic stem cell (ESC) and germline data and apply to adult mouse organs at steady-state or during regeneration. Here, we use molecule counting and spike-in normalization to develop absolute scaling of single-cell RNA sequencing data.
This limitation is in large part due to the fact that modern sequencing approaches, including single-cell RNA sequencing (scRNA-seq), generally assume similar levels of transcriptional output per cell. Despite its potential widespread relevance, documented examples of hypertranscription remain few and limited predominantly to early development. Hypertranscription facilitates biosynthetically demanding cellular state transitions through global upregulation of the nascent transcriptome.
0 kommentar(er)
