20 years of stemness: From stem cells to hypertranscription and back

Transcriptional profiling of stem cells came of age at the beginning of the century with the use of microarrays to analyze cell populations in bulk. Since then, stem cell transcriptomics has become increasingly sophisticated, notably with the recent widespread use of single-cell RNA sequencing. Here, we provide a perspective on how an early signature of genes upregulated in embryonic and adult stem cells, identified using microarrays over 20 years ago, serendipitously led to the recent discovery that stem/progenitor cells across organs are in a state of hypertranscription, a global elevation of the transcriptome. Looking back, we find that the 2002 stemness signature is a robust marker of stem cell hypertranscription, even though it was developed well before it was known what hypertranscription meant or how to detect it. We anticipate that studies of stem cell hypertranscription will be rich in novel insights in physiological and disease contexts for years to come.