An essential and almost existential question regarding cancer development has been a matter of intense debate in the past year. Environmental insults such as ultraviolet radiation, smoking or others were recently proposed to account for only a small portion of cancer risk, and we were offered an alternative ‘bad luck’ hypothesis.1 Bad luck was more likely to occur in highly replicative and long-lived cells that could maintain and propagate a given mutation. This question is of utmost importance and at the centre of preventive efforts against cancer.

In a recent publication, Zhu et al. addressed this issue through genetic labelling and tracking of cells with either high or low stem cell potential.2 Indeed lineage tracing is one of the main tools in determining cell fate or the cell of origin of cancer.3, 4 It has been used in a variety of cancer types to specifically label or induce an oncogenic event in a precise candidate cell population to be followed. Zhu et al. decided to target a CD133+ population that admittedly would play different roles in different organs. From the lack of tissue or stem cell specificity of this marker emerges the actual originality of this study. Indeed, in a first series of experiments they characterized how important the CD133+ population was in contributing to the homeostasis and development of the tissue of interest. This was performed through lineage tracing and labelling of CD133+ cells in the neonatal or adult period and following their fate over time to find whether they’ve formed part or most of the tissue. From this first experiment the authors concluded that CD133+ cells were acting as stem cells in some tissues but as differentiated cells without stem cell properties or ‘generative capacity’ in others. This apparent heterogeneity in function among CD133+ cells was then used to interrogate the potential of CD133+ cells to generate tumours by genetically introducing a wide range of potential activated oncogenes or inactive tumour suppressors.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD