Thesis Defense Yorick Post: “Modeling Vertebrate Adult Stem Cells and Their Progeny”

The adult body consists of trillions of cells. These cells form the building blocks for all organs and tissue in the body. Cells are constantly lost at different speeds due to natural turnover or damage. For example, cells in intestinal tissue live for about five days and cardiac muscle cells – also called cardiomyocytes – survive for up to a lifetime. When cells are lost, they need to be replaced. Adult stem cells have the capacity to replace lost cells through cell division.

Organ recovery

Most organs in the human body possess adult stem cells. These cells function according to the organ in which they are present; an intestinal stem cell only produces intestinal cells, while a liver stem cell only makes liver cells. When cells in a certain organ are lost, stem cells divide and produce offspring: new cells to replace the lost ones. The presence of stem cells often determines how quickly and efficiently an organ recovers after damage.

During his PhD, Post developed model systems for adult stem cells and their offspring. Such research into the identity and function of adult stem cells contributes to our understanding of how organs function on a cellular level and offers insight into what goes wrong during disease.

Cardiac infarct

Post used a technique called lineage tracing: he marked cells that engage in cell division, and their offspring, with a fluorescent color. This technique allowed Post and colleagues to trace the origin and establish the identity of proliferating (dividing) cells and their progeny. He employed lineage tracing in neonatal and adult hearts of mice, as well as hearts that suffered damage. In combination with a technique called single cell sequencing, the team identified the cell populations that are important for heart recovery after cardiac damage caused by, for example, an infarct.

Organoids from snake and human

Every animal, and every organ, exploits adult stem cells and replaces lost tissue in their own way. Post used organoid technology to grow miniature versions of organs of various vertebrates in the lab, such as snake venom gland organoids and human lacrimal gland organoids. These mini organs, also called organoids, are 3D structures of about half a mm in size grown from adult stem cells. Using the organoids that he developed, Post and colleagues studied organ function in a variety of vertebrates, from reptile to human. The team used adult stem cells directly from snakes to cultivate venom gland organoids. They discovered that these organoids produce functional venom that can be collected. The miniature venom glands therefore form a foundation for venom production in the lab and provide opportunities for the development of antivenom and other venom-related medicines.

Stem cell potential

Post’s thesis describes new experimental models to study vertebrate adult stem cells and lifts the veil on their potential for research and beyond.