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Chromaffin progenitor cells in adrenal tissue formation

Fachliche Zuordnung Endokrinologie, Diabetologie, Metabolismus
Förderung Förderung von 2011 bis 2018
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 189897882
 
The adult adrenal medulla contains progenitor cells. We aim to understand their precise role in the adrenals capacity to adapt to physiological needs, tissue plasticity and tumor formation. Therefore, in the first funding period, we studied three key aspects of these cells: (1) In vitro and in situ analysis of progenitor cells from nestin- GFP reporter mice revealed their differentiation potential to the chromaffin, glial, and neural lineages; (2) Immobilization stress reduced their number indicating an involvement in stress adaptation; (3) Finally, we identified a new signaling pathway (STAT3-Ser/Hes3) that regulates both cell number and catecholamine content in vitro and might play a key role in the process of stress adaptation. Based on this work, we will now address the fate specification and signaling requirements of these progenitor cells in the normal and stressed mouse (immobilization and sepsis models). Specifically: (1) We will characterize adult adrenal progenitors for biomarker expression and fate specification using an inducible nestin-YFP reporter mouse line allowing for a detailed kinetic study; (2) We will determine the relevance of Hes3 in vivo on adrenal function (catecholamine production, adrenal tissue formation) using a Hes3 null mouse line. This work will uncover in vivo functions of adrenal medullary progenitors essential to the function of the adrenal medulla and will form the basis for understanding mechanisms of stress related adrenal tissue formation and disorders.
DFG-Verfahren Klinische Forschungsgruppen
 
 

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