Transcriptional Profiling of Quiescent Muscle Stem Cells In Vivo

• Published in: Cell reports (Cambridge) Vol. 21; no. 7; pp. 1994 - 2004
• Main Authors: van Velthoven, Cindy T.J., de Morree, Antoine, Egner, Ingrid M., Brett, Jamie O., Rando, Thomas A.
• Format: Journal Article
• Language: English; Norwegian
• Published: United States Elsevier Inc 14.11.2017; Cell Press; Elsevier
• Subjects: Animals; Gene Expression Profiling - methods; Gene Expression Profiling - standards; Male; Mice; Mice, Inbred C57BL; Myoblasts - cytology; Myoblasts - metabolism; nascent transcription; quiescence; satellite cells; Transcriptome; nascent transcription; quiescence; satellite cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.10.037

Muscle stem cells (MuSCs) persist in a quiescent state and activate in response to specific stimuli. The quiescent state is both actively maintained and dynamically regulated. However, analyses of quiescence have come primarily from cells removed from their niche. Although these cells are still quiescent, biochemical changes certainly occur during the isolation process. Here, we analyze the transcriptome of MuSCs in vivo utilizing MuSC-specific labeling of RNA. Notably, labeling transcripts during the isolation procedure revealed very active transcription of specific subsets of genes. However, using the transcription inhibitor α-amanitin, we show that the ex vivo transcriptome remains largely reflective of the in vivo transcriptome. Together, these data provide perspective on the molecular regulation of the quiescent state at the transcriptional level, demonstrate the utility of these tools for probing transcriptional dynamics in vivo, and provide an invaluable resource for understanding stem cell state transitions. [Display omitted] •Quiescent MuSCs show widespread, low-level, active transcription in vivo•Dynamic regulation of subsets of transcripts occurs in MuSCs in vivo•Induction of stress response transcriptional programs accompanies MuSC activation•Both active transcription and degradation control transcript levels in activating MuSCs van Velthoven et al. use metabolic labeling of RNA to examine the quiescent transcriptome of MuSCs in vivo and during early activation. They find dynamic regulation of specific subsets of transcripts in quiescent and activating MuSCs, and they demonstrate the utility of these tools for probing transcriptional dynamics in vivo.