Hypertranscription: the invisible hand in stem cell biology.

Hypertranscription occurs when cells upregulate gene expression across the majority of the transcriptome, including at housekeeping and other ubiquitously expressed genes. Although masked by standard normalization procedures, hypertranscription can be detected using modifications to sample preparation and normalization of sequencing data. Originally characterized in embryonic stem cells, recent advances have identified hypertranscription to be pervasive in stem cells across development, reprogramming, organ homeostasis, and tissue regeneration. These contexts share unified mechanistic features of hypertranscription, many of which are redeployed in hypertranscribing cancer cells. As a counterpart to the hypertranscriptive state, emerging evidence suggests that global downregulation of transcriptional output to enter hypotranscription is a key component of embryonic diapause and stem cell quiescence, possibly also being co-opted by dormant cancer cells to survive chemotherapy. Stem cells are the fundamental drivers of growth during development and adult organ homeostasis. The properties that define stem cells – self-renewal and differentiation – are highly biosynthetically demanding. In order to fuel this demand, stem and progenitor cells engage in hypertranscription, a global amplification of the transcriptome. While standard normalization methods in transcriptomics typically mask hypertranscription, new approaches are beginning to reveal a remarkable range in global transcriptional output in stem and progenitor cells. We discuss technological advancements to probe global transcriptional shifts, review recent findings that contribute to defining hallmarks of stem cell hypertranscription, and propose future directions in this field. [ABSTRACT FROM AUTHOR]