Defining hallmarks of stem cells

Afrom Roche’sand Rochedescribes stem cells’ unique and shared features, laying the foundation of what is known in the stem cell universe and mapping  new approaches in drug discovery

Much like stars that give rise to galaxies, stem cells hold the power to generate an array of specialized cells, shaping the biological universe within our bodies. Researchers have spent the last few decades seeking to understand that power of stem cells that can help our bodies recover from injuries and grow or regrow tissue  — and that also serve as the starting point for making new models to study disease and potential treatments in the lab. 

Now, Roche Senior Scientist of the Institute of Human Biology Joep Beumer and Head of pRED Hans Clevers have delivered a high-profilein the journal Cell Stem Cell of these efforts to date, uncovering some exciting mysteries, charting the way to intriguing new research avenues, and finding common ground among the many types of stem cells in our bodies: defining the “Hallmarks” of stem cells.

But first, what defines a stem cell? Early definitions and expectations of what stem cells are, and what they are capable of, were heavily shaped by insights derived from stem cells in the blood, followed by identifying and characterizing stem cells of particular tissues, like gut and skin. Yet many of the features defined as inherent to stem cells from the earliest studies turn out not to be true across the board. Different tissues in our body have different kinds of stem cells with features that are adapted to their unique environment, and the tissue they support. Beumer and Clevers parsed the differences and similarities across these cell types to define six universal hallmarks of stem cells, regardless of what tissue they come from.

Understanding stem cells matters not only because they are part of our bodies, but also because they are key to an important technology that benefits patients: organoid models. Made from human stem cells, organoids can often more faithfully replicate the interactions among different cell types within an organ in disease than animal models, allowing researchers to test the safety and effectiveness of new therapies in the lab. Excitingly, patients’ own stem cells can be turned into organoids of different tissues, allowing for a personalized medicine approach. This strategy has already been used to probe the effectiveness of certain COVID-19 treatments and to identify patients who would benefit from specific cystic fibrosis drugs, and is poised to make an even larger impact on drug discovery and therapy in years to come. For example, organoid transplantation is already being considered as a potential therapy, with the firstof salivary gland organoids already under way.

But to make the best organoids that most reliably replicate what might happen in a patient’s body, scientists need to completely understand the universe of stem cells. The goal of the “Hallmarks” review is to guide this inquiry, collating what is known so far and defining key questions going forward. One essential area to explore further is the environment stem cells live in, known as the “niche,” which is unique to each stem cell type. Doing so will allow researchers to make the right organoid for different questions and purposes, explained Beumer.

Improving our understanding of the stem cell hallmarks will ultimately lead to better organoid models, expanding their use cases, Beumer added. While some of this work will continue to be done in university labs, it is also the focus of Roche’s new Institute of Human Biology, where Beumer leads the Organoid Gene Editing group. Uniquely combining top academic style research with access to Roche’s translational data and resources, the IHB is focused on accelerating drug discovery through the further development and use of organoid technology.

Just as the first key “hallmarks” paper in biology, “Hallmarks of Cancer” by noted biologists Douglas Hanahan and Robert Weinberg, helped chart the constellation  of cancer research since the article was published in 2000, Beumer and Clevers hope that the “Hallmarks” of stem cells review will stimulate discussion and research in the field, not only increasing open-mindedness about what stem cells can be, but also driving organoid technology forward for patients. 

Journal review paper is available open access: Joep Beumer and Hans Clevers (2024). Hallmarks of stemness in mammalian tissues. Cell Stem Cell. 31(1):7-24.

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