[RESEARCH HIGHLIGHTS]


| RESEARCH HIGHLIGHTS |


Microscopy image of the underside of a pyloric gland showing fluorescently labeled cells.


Stem cells:


TRACKING STEM CELLS IN THE STOMACH LINING


STEM CELL BEHAVIOR REVEALED BY A COMBINATION OF MODELING AND MICROSCOPY


The renewal of cells in a healthy stomach is being studied by A*STAR researchers through a multidisciplinary approach that combines cell lineage tracing experiments and mathematical modeling1. The models provide a valuable baseline for studying gastric diseases, and the approach can be used to investigate the developmental dynamics of other organs. Nick Barker’s team at the A*STAR Institute


of Medical Biology studied the development of flask-shaped pockets in the lining of the stom- ach’s pyloric region, known as pyloric glands, which secrete gastrin and mucus into the stomach. Within each gland is a dividing pool of stem cells that contributes to two essential


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processes. Some of the daughter cells remain undifferentiated and slowly replace other stem cells within the gland, while others migrate upwards and differentiate to renew the stomach lining relatively rapidly. The researchers used stochastic models to study these two processes, using observations of fluorescently labeled cells to fit the models. Since stem cells divide and replace other


stem cells, eventually all of the cells in a gland will have descended from a single stem cell. To investigate this process, the team extended an earlier model that assumed the process starts with a single stem cell, rather than a pool. By building a model without this assumption, the


team discovered that only a few of the stem cells are in a position for their descendants to effectively expand to the entire gland. The researchers also quantified the


renewal of the stomach lining by stem cell proliferation and differentiation. By integrating stochastic models and


experiments they showed that the processes of proliferation and differentiation are tightly coupled; stem cells normally divide at the same rate as their daughters differentiate, ensuring that the pool remains the same size. The team also applied this approach to


quantify stem cell proliferation and differenti- ation under conditions that resembled disease,


A*STAR RESEARCH 25


© 2016 A*STAR Institute of Medical Biology


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