SCORPION: Stem Cells, Tissues, Organoids – Dissecting Regulators of Potency and Pattern Formation

The SCORPION collaborative program delivered discoveries that have significant implications for understanding how stem cells operate, how tissues regenerate, and how organoid models can be used to study human development and disease. The Bücker lab studied how single stem cells transition out of a pluripotent state-the point where they can become any type of cell in the body. They identified specific markers which are crucial for tracking when and how cells commit to a particular developmental path. Building on this, the Leeb team made strides in understanding the genetic underpinnings of how stem cells make these decisions and identified several genes that play key roles in guiding differentiation. They manipulated these genes, shedding light on the broader mechanisms that drive early lineage commitment in embryonic stem cells. In invertebrate models, Technau's team focused on the sea anemone Nematostella vectensis. They discovered how Notch signaling is essential for the self-organisation process and regeneration in gastruloids. Raible's research on the marine bristle worm Platynereis dumerilii revealed how the stem cells underlying postlarval growth re-emerge when experimentally removed. They found that differentiated cells revert to a more stem cell-like state, also involving the myc gene. In similar work performed in the Mexican salamander, the axolotl, the Tanaka group tracked individual cells in the regenerating limb. Also in this system, cells revert to a more stem cell-like state before rebuilding the missing tissue. The Urbn group explored how adult neural stem cells are affected by diet and metabolism. Using mouse models, they discovered that certain metabolic conditions, such as those induced by calorie restriction or a high-fat diet, can either promote or inhibit the activation of these stem cells. A major innovation in organoid research came from Knoblich's lab, where the team developed more sophisticated models of the human brain by using bioengineered scaffolds which help guide the development of cerebral organoids-small, three-dimensional models of brain tissue-so they more accurately mimic the structure and function of the human brain. Together with the Mendjan group they investigated how different types of fat tissue and their associated blood vessels develop together. By co-culturing human stem cells into both fat cells and vascular cells, they modeled how these tissues interact during development. Lastly, Koo's research revealed the importance of stem cell diversity in maintaining the stomach's lining and identified two distinct populations of stem cells that reside in different parts of the stomach. While both types of cells contribute to normal tissue maintenance, they respond differently to injury, revealing how the body balances tissue repair and homeostasis.