Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1X5, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1X5, Canada.
Cell Rep. 2023 Jan 31;42(1):111978. doi: 10.1016/j.celrep.2022.111978. Epub 2023 Jan 11.
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.
转录过表达通过全局转录组上调支持生物合成需求高的细胞状态。尽管其潜在的相关性很广泛，但有记录的转录过表达的例子仍然很少，仅限于早期发育。在这里，我们证明了单细胞 RNA 测序数据的绝对缩放可以估计每个细胞的总转录本丰度。我们在已知的发育转录过表达的情况下验证了绝对缩放，并将其应用于成体细胞类型，揭示了转录输出的显著动态范围。在成年器官中，转录过表达标记具有多能性的激活干细胞/祖细胞，并在组织损伤的情况下重新分配，在再生过程中，它先于增殖爆发。我们的分析确定了一组与成体和胚胎转录过表达都相关的常见分子途径，包括染色质重塑、DNA 修复、核糖体生物发生和翻译。这些在不同细胞环境中共享的特征支持转录过表达作为一种普遍存在的、动态的细胞程序，在发育、器官维持和再生过程中广泛使用。
