Abstract
The enteric nervous system (ENS) controls and modulates gut motility and responds to food intake and to internal and external stimuli such as toxins or inflammation. Its plasticity is maintained throughout life by neural progenitor cells within the enteric stem cell niche. Granulocyte-colony stimulating factor (G-CSF) is known to act not only on cells of the immune system but also on neurons and neural progenitors in the central nervous system (CNS). Here, we demonstrate, for the first time, that G-CSF receptor is present on enteric neurons and progenitors and that G-CSF plays a role in the expansion and differentiation of enteric neural progenitor cells. Cultured mouse ENS-neurospheres show increased expansion with increased G-CSF concentrations, in contrast to CNS-derived spheres. In cultures from differentiated ENS- and CNS-neurospheres, neurite outgrowth density is enhanced depending on the amount of G-CSF in the culture. G-CSF might be an important factor in the regeneration and differentiation of the ENS and might be a useful tool for the investigation and treatment of ENS disorders.
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Acknowledgments
We thank Sandra Schrenk for help with the primary cell culture and Franziska Markwart for support with cryostat sections and staining. We are grateful to Norbert Pütz from the group of Prof. Dr. Gunther Wennemuth, Department of Anatomy, University Clinic Homburg, for aid with immunogold labeling and to Prof. Dr. Frank Kirchhoff, University Clinic Homburg, for providing GFAP-GFP-transgenic mice. We also thank Dr. Cornelia Hagl, Dr. Holger Rabe and David Grundmann for proofreading the manuscript.
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This study was supported by the German Ministry of Education and Research, BMBF, FKZ 17114X10.
The authors declare no conflicts of interest.
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Schuster, A., Klotz, M., Schwab, T. et al. Granulocyte-colony stimulating factor: a new player for the enteric nervous system. Cell Tissue Res 355, 35–48 (2014). https://doi.org/10.1007/s00441-013-1744-1
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DOI: https://doi.org/10.1007/s00441-013-1744-1