Cell biology of stem cells: studying stem cells at the level of cell biology and studying cell biology using stem cells.

The field of stem cell biology has been enjoying a period of considerable activity and progress. The therapeutic potential of pluripotent stem cells has sparked public interest to the point that probably many life scientists have been asked at some point by lay people whether they work with stem cells, even when those people do not understand what the term “stem cells” means. There is much excitement in stem cell research because it holds great promise both for its therapeutic potential and for its utility for studies of cell biology.

The stem cell field has become a modern alchemy—it sometimes seems that if you mix things up in the right order and proportions something magical will happen, leading to cures for all diseases and new insights into basic biological mechanisms. Is this true? It is important to bear in mind that the original alchemy was also supported by quite a bit of evidence-based science: generation of certain compounds, which “looked like” they would lead to the eventual generation of gold, were scientifically proven. Fortunately, stem cell biology has a bit better promise than alchemy: we can generate pluripotent stem cells, and these stem cells can differentiate into many cell types in adult tissues. Thus, the challenge now is to harness the potential of stem cells for therapeutic uses and basic research.

Work toward realization of the potential utility of stem cells has shown us how much we have yet to learn about them. Although stem cells can be defined by their functionality, that is, their ability to produce differentiated cells continuously to populate tissues while maintaining their identity and pluripotency, much is yet to be learned before we will understand which cellular processes support this ability. Accordingly, many researchers are pouring their efforts into understanding the behaviors and characteristics of natural stem cells (e.g., tissue-specific stem cells). In this effort, the long history of cell biology has become a rich source of information for understanding stem cell behavior. After all, to state the obvious, stem cells are cells. Therefore, the toolkits that stem cells use to achieve their functionality have their basis in well-studied cell biology systems: determinants of when stem cells divide, how they replicate and repair DNA, and how they segregate chromosomes during mitosis are the same determinants used in all eukaryotic cells. Accordingly, deep and broad knowledge in cell biology is essential for stem cell biologists.

In parallel, stem cell technologies and resources have started to provide fertile territory for cell biology research. The cell biology field has long relied on a limited number of immortalized cell lines, which we now recognize to be quite different from normal cells. The ability to generate induced pluripotent stem (iPS) cells from essentially any cell type, and to then differentiate them back into specific cell types of one’s choice, has expanded the horizons of many fields of cell biology. iPS cell technology provides researchers with better control over cell lineage, isogenticity, and cell physiology, facilitating comparisons of results (e.g., “wild type” and “mutant” cells can have precisely the same genetic backgrounds). Additionally, the generation of iPS cells from patients (sometimes followed by the cells’ differentiation into a particular cell type or even organoids) has provided a unique opportunity to understand the cellular basis for pathology. As the stem cell technologies expand the scope of what can be done in studies of cell biology, cell biologists face new challenges in deciding what to study and in what contexts.

Despite the clear importance of communication between cell biologists and stem cell biologists, and despite efforts to enhance this communication, there is still much that can be done to further promote the integration of basic cell biology and stem cell biology research. Recognizing the importance of enhancing these lines of communication, Molecular Biology of the Cell has launched this special issue on the Cell Biology of Stem Cells. In addition to original articles that are published in this special issue, we have also curated a list of stem cell–related papers from articles published previously in Molecular Biology of the Cell. This effort was led by special issue editors Dianne Barber, Terry Lechler, Jason Spence, David Traver, and myself. We look forward to continuing our support of the field of stem cell biology in the coming years.