A new way to identify dormant cells
June 6, 2021—At any given moment, most cells in the human body are not dividing. Some are permanently in that state whereas others, such as adult stem cells, can re-enter the proliferative state in response to certain triggers, like the need to repair damaged tissue. These reversibly non-dividing cells—so-called dormant cells—are important for tissue homeostasis, repair and regeneration, for example in the gut. In malignant tumors, meanwhile, dormant cancer cells can evade therapies that target fast-dividing cells and seed future disease recurrence.
Existing methods to identify dormant stem cells rely on distinct surface markers found on specific types of stem cells, rather than a general identifier that is independent of tissue type or species. Such methods also require prior knowledge of the stem cell population of interest that precludes their use for the discovery of new stem cell types.
In this Nature Communications paper, Rasmus Freter and colleagues from the laboratories of Ludwig Oxford’s Colin Goding and Francesco Neri of Friedrich-Schiller-University, in Jena, Germany, set out to develop a more general method for identifying dormant stem cells that would be applicable to all cell types, including cancerous ones, and which would not rely on pre-existing knowledge of the location of the stem cells. To do so, they made use of the fact that dormant stem cells have low activity of CDK9, an enzyme essential to gene activation and expression.
The researchers designed a genetically encoded assay for CDK9 activity called Optical Stem Cell Activity Reporter (OSCAR) that fluoresces in dormant stem cells but not in cells with active CDK9. OSCAR, they showed, could reveal dormant stem cells in time-lapse microscopy of intestinal organoid cultures, in an OSCAR mouse model, and by fluorescence-activated cell sorting.
This method provides a useful tool for characterising dormant cells in cultured cells and in living tissues, including cancers. The ability to isolate live dormant cells, understand why they are dormant and how they are reactivated will be an asset to both regenerative medicine and the development of novel anti-cancer therapies.