Non-mammalian model organisms generally delay ZGA until after several cell divisions of the embryo, and aspects such as the dilution of maternal factors or cell cycle length contribute to the onset of ZGA. that the rest of the transcriptome is largely unchanging, or housekeeping. While this allows for the identification of highly tissue- or state-specific developmental regulators, it can provide an incomplete picture of the ways in which the transcriptomes of distinct cell types differ. There can be major differences in functions that are often considered as housekeeping between stem cells and their differentiated progeny, or even between different states of the same stem cell type. For example , energy metabolism can vary greatly in stem cells depending on their state or age (Ito and Suda, 2014; Mohrin et al., 2015; Zhou et al., 2012). Moreover, recent Saridegib studies indicate that stem cells can exist in a state of hypertranscription, which may also be called hyper-active LRRC48 antibody transcription (Efroni et al., 2008) or transcriptional amplification (Lin et al., 2012; Nie et al., 2012). This state is associated with a particularly open, permissive chromatin structure (Efroni et al., 2008; Gaspar-Maia et al., 2011; Meshorer et al., 2006). Hypertranscription can be defined as the coordinate increase in the nascent output of the majority of the transcriptome, including housekeeping genes such as those coding for ribosomal proteins (Guzman-Ayala et al., 2015; Mattout and Meshorer, 2010). A concomitant increase in the synthesis of ribosomal RNA, the major RNA fraction in the cell, is also a component of hypertranscription. This increase in nascent transcriptional output may be relative to an earlier or subsequent developmental stage, or to neighboring cells, and is often associated with an increase in cell proliferation (Guzman-Ayala et al., 2015; Koh et al., 2015; Nie et al., 2012). Hypertranscription is therefore defined here in a relative and never an absolute sense. The goal of this review is to prompt researchers to consider analyzing hypertranscription in their developmental contexts of interest, and the accumulation of further studies may in the future help refine the definition of hypertranscription. While the regulation of RNA stability can contribute to changes in steady-state levels of transcripts, for clarity we propose that the term hypertranscription be used to refer to cases where there is a global elevation in nascent transcription. As documented in the examples reviewed below, hypertranscription may be essential to fuel the biosynthetic demands of rapidly growing stem and progenitor cells during development. Evidence suggestive of hypertranscription has been present for many decades. The pioneering German biologist Walther Flemming, who studied the behavior of chromosomes at mitosis and coined the term chromatin, described in 1882 a very peculiar structure of the chromosomes Saridegib in growing amphibian Saridegib oocytes (Fig. 1a). It took until the 1960s for these structures, called lampbrush chromosomes, to be shown as corresponding to sites of high levels of transcription (Callan, 1987; Flemming, 1882). In addition , by the 1940s, it was already known that the levels of RNA can vary widely in different cell types. Working in Sweden prior to and during World War II, Torbjrn Caspersson and his student Bo Thorell observed that rapidly dividing undifferentiated cells, including embryonic cells and blood progenitors, have increased levels of RNA relative to adult cells (Caspersson and Schultz, 1939; Thorell, 1947) (Fig. 1b). Jean Brachet, a pioneering molecular embryologist from Belgium, reached similar conclusions around the same time (Brachet, 1947). Caspersson and Thorell speculated that this elevation in RNA levels in progenitor cells, often associated with a large nucleolus, was due to a hyperfunction of chromatin (Caspersson, 1941; Caspersson and Thorell, 1941) (Fig. 1c), a designation strikingly similar to the term hypertranscription currently in use. Shortly thereafter, the amount of RNA per cell was shown to be higher in cancer cells relative to their normal counterparts (Petermann and Schneider, 1951; Thorell, 1947; Weymouth et al., 1955). Of course none of these studies acknowledged the centrality of RNA in the flow of genetic information Saridegib in cells, as they were carried out before the structure of DNA was discovered or the genetic code was deciphered. Paradoxically, with the molecular biology revolution and more recently in the genomics era, hypertranscription has gone largely undetected. This is because standard gene expression profiling methods tend to mask global shifts in transcription. The recent discovery that overexpression of cMyc can induce a global amplification of transcriptional output (Lin et al., 2012; Lovn et al., 2012; Nie et al., 2012) has revived an interest in hypertranscription. These findings have contributed to the ongoing exploration of the potential therapeutic benefit.