Abstract: Self-organization of two-dimensional colonic monolayers as a model system for pattern formation

Abstract: Self-organization of two-dimensional colonic monolayers as a model system for pattern formation

The establishment and maintenance of spatially separated cell compartments, or pattern formation, is a universal feature of multicellular organisms and is essential for performing the many complex functions required for multicellular life. Patterning is especially evident in the human colon, where tissue homeostasis is maintained by stem cells in crypt structures that balance proliferation and differentiation and are spatially separated from fully differentiated cells in the lumen.  Roughly 10 million evenly spaced crypts separated by differentiated cells inhabit the human colon and are renewed every 3-5 days. Turnover is due to cell extrusion and death which is largely confined to the differentiated cell compartment, while cell division, required to replace differentiated cells, is restricted to the crypts. How information is passed from the differentiated compartment to the stem cell crypts to maintain regular spacing is unknown. We recently developed a patient-derived organoid system that self-organizes into evenly spaced crypt structures separated by differentiated cells in a two-dimensional monolayer which is amenable to high content imaging. Using this system, we found that death of differentiated cells initiates a wave of Erk Kinase activity that spreads radially from dead cells and causes differentiation of stem cells in the crypt.