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Postnatal human enteric neurospheres show a remarkable molecular complexity
Author(s) -
Schmitteckert Stefanie,
Mederer Tanja,
Röth Ralph,
Günther Patrick,
HollandCunz Stefan,
Metzger Marco,
Samstag Yvonne,
SchröderBraunstein Jutta,
Wabnitz Guido,
Kurzhals Stefan,
Scheuerer Jutta,
Beretta Carlo A.,
Lasitschka Felix,
Rappold Gudrun A.,
Romero Philipp,
Niesler Beate
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13674
Subject(s) - neurosphere , enteric nervous system , stem cell , progenitor cell , biology , neural stem cell , multipotent stem cell , neurogenesis , neural crest , neuroscience , immunology , microbiology and biotechnology , adult stem cell , cellular differentiation , gene , genetics , embryo
Abstract Background The enteric nervous system (ENS), a complex network of neurons and glial cells, coordinates major gastrointestinal functions. Impaired development or secondary aberrations cause severe enteric neuropathies. Neural crest–derived stem cells as well as enteric neuronal progenitor cells, which form enteric neurospheres, represent a promising tool to unravel molecular pathomechanisms and to develop novel therapy options. However, so far little is known about the detailed cellular composition and the proportional distribution of enteric neurospheres. Comprehensive knowledge will not only be essential for basic research but also for prospective cell replacement therapies to restore or to improve enteric neuronal dysfunction. Methods Human enteric neurospheres were generated from three individuals with varying age. For detailed molecular characterization, nCounter target gene expression analyses focusing on stem, progenitor, neuronal, glial, muscular, and epithelial cell markers were performed. Corresponding archived paraffin‐embedded individuals' specimens were analyzed accordingly. Key Results Our data revealed a remarkable molecular complexity of enteric neurospheres and archived specimens. Amongst the expression of multipotent stem cell, progenitor cell, neuronal, glial, muscle and epithelial cell markers, moderate levels for the pluripotency marker POU5F1 were observed. Furthermore, besides the interindividual variability, we identified highly distinct intraindividual expression profiles. Conclusions & Inferences Our results emphasize the assessment of molecular signatures to be essential for standardized use, optimization of experimental approaches, and elimination of potential risk factors, as the formation of tumors. Our study pipeline may serve as a blueprint implemented into the characterization procedure of enteric neurospheres for various future applications.