Identification and characterization of enteric nervous system stem cells

Projektbeschreibung

Zelluläre und molekulare Charakterisierung des „Bauchhirns“

Das enterische Nervensystem ist das intrinsische Nervensystem des Darms und kleidet die Wände des Magen-Darm-Trakts aus. Es interagiert mit der Aktivität des intestinalen Immunsystems, der Epithelbarriere und der Mikrobiota, um die Homöostase im Darm zu steuern. Das Ziel des EU-finanzierten Projekts IDENSTEM besteht in der Charakterisierung der zellulären Mechanismen, welche der Funktion des enterischen Nervensystems zugrunde liegen. Die Forschenden werden sich auf eine spezifische Population enterischer Gliazellen konzentrieren und deren Funktionsweise im stabilen Zustand sowie in Reaktion auf eine Verletzung untersuchen. Zudem besteht richtet sich ihr Interesse darauf, den Beitrag dieser Zellen zu Darmentzündungen zu erforschen, die für viele Darmerkrankungen kennzeichnend sind.

Ziel

The digestive system is essential for water and nutrient uptake, waste removal and serves as a sensory system providing information to the central nervous system via the gut-brain communication axis. The gastrointestinal tract harbours the largest collection of neurons and glial cells collectively known as the enteric nervous system (ENS) and regulate digestive physiology independently of brain input. Intestinal function and homeostasis depend on the integrated and balanced activity of multiple gut tissues,in which, the ENS plays a critical role by actively interacting with the intestinal immune system, the epithelial barrier and microbiota. Developmental deficits or acquired disorders in any of these tissue components can result in debilitating gastrointestinal conditions, such as Hirschsprung disease (congenital megacolon) or inflammatory bowel disease. Despite critical contributions of the ENS to digestive physiology and intestinal homeostasis, very little is known about the cellular mechanisms that underpin its function at steady state conditions or in response to injury. IDENSTEM will address the identity and properties of ENS neural stem cells (ENSCs) using the mouse as an experimental model organism. Preliminary data suggest that a subpopulation of enteric glial cells expressing the Notch signalling target Hes5, undergo low rate proliferation and exhibit neurogenic potential. In this proposal, we aim to identify and characterize the cellular and molecular properties of this population. We wish to understand their contribution in maintaining ENS integrity under normal conditions or in response to injury/disease. These studies will advance fundamental neurogastroenterology and the development of novel therapeutic strategies for various gut disorders. Furthermore, they will provide insight into ENS contributions to the gut tissue circuitry and in intestinal inflammation. IDENSTEM will open a new window of knowledge to improve human health.