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Adult stem cells exhibit global suppression of RNA polymerase II serine-2 phosphorylation

Rasmus Freter1, Masatake Osawa, Shin-Ichi Nishikawa

  • 1Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. rasmus.freter@ludwig.ox.ac.uk

Stem Cells (Dayton, Ohio)
|July 20, 2010
PubMed

Insights

Adult stem cells conserve energy and protect themselves from damage by pausing mRNA transcription. This quiescent state, characterized by the absence of RNA polymerase II phosphorylation, is a conserved feature across various stem cell types.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Stem Cell Biology

Background:

  • Adult stem cells are crucial for tissue repair and homeostasis.
  • Their quiescent state, a reversible cell cycle arrest, is poorly understood.
  • Previous work indicated downregulated housekeeping gene expression in melanocyte stem cells (MelSCs).

Purpose of the Study:

  • To investigate the molecular mechanisms of adult stem cell quiescence.
  • To determine if suppressed mRNA transcription is a general characteristic of adult stem cells.
  • To explore the role of RNA polymerase II (RNApII) and its associated kinases in stem cell quiescence.

Main Methods:

  • Utilized antibodies against phosphorylated RNA polymerase II (RNApII) to assess transcriptional activity.
  • Examined RNApII phosphorylation status in various adult stem cell types (MelSCs, keratinocytes, muscle, spermatogonia, hematopoietic stem cells).
  • Investigated the role of CDK9, an RNApII kinase, in stem cell function and survival.

Main Results:

  • Adult MelSCs and other tested adult stem cells showed an absence of productive mRNA transcription elongation.
  • RNApII was initialized but not actively elongating mRNA in quiescent stem cells.
  • CDK9, a key kinase for transcription elongation, was absent in adult MelSCs and other stem cells.
  • CDK9 inhibition enhanced the survival of cells deprived of survival factors.

Conclusions:

  • The absence of productive mRNA transcription is a conserved, specific, and early characteristic of adult stem cells.
  • This transcriptional quiescence may reduce metabolism and protect against cellular/genetic damage.
  • Identifying transcriptionally quiescent cells could lead to the discovery of stem cell-like phenotypes in various tissues, including tumors.

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