Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch

Abstract

Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells—including germline stem cells—become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions—GLP-1/Notch signaling—becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

DOI: http://dx.doi.org/10.7554/eLife.10832.001

eLife digest

Adult stem cells can divide to produce cells that can develop into one of many different specialist cell types in a tissue, and so are vitally important for tissue repair and maintenance. Some types of adult stem cells exist primarily in a non-dividing state known as quiescence, which for a long time was thought to be essential for maintaining the stem cell state. However, researchers have discovered some adult stem cells that are either not quiescent, or only enter this state rarely.

Until now, biologists have lacked an experimental model in which the role of quiescence in maintaining stem cells can be easily investigated. Seidel and Kimble have now investigated the role of quiescence in the germline stem cells – which give rise to egg and sperm cells – of the roundworm Caenorhabditis elegans. The results of the study revealed that although the germline stem cells divide continuously when the worms are well fed, starving the worms causes these stem cells to become quiescent.

Maintaining C. elegans germline stem cells in a stem cell state normally involves a process called Notch signaling, which cells use to communicate with each other. However, Seidel and Kimble found that the germline quiescence caused by starvation maintains the stem cell state even when Notch signaling is prevented. This suggests that, in the absence of food, quiescence alone can maintain germline stem cells, although how it does so remains a question for future work. One possibility is that quiescence stabilizes other molecules involved in the Notch signaling pathway or prevents the production of proteins that enable a stem cell to develop into a specialized cell.

DOI: http://dx.doi.org/10.7554/eLife.10832.002