title: Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-κB Activation.
abstract: Brain inflammation, a common feature in neurodegenerative diseases, is a complex series of events, which can be detrimental and even lead to neuronal death. Nonetheless, several studies suggest that inflammatory signals are also positively influencing neural cell proliferation, survival, migration, and differentiation. Recently, correlative studies suggested that astrocytes are able to dedifferentiate upon injury and may thereby re-acquire neural stem cell (NSC) potential. However, the mechanism underlying this dedifferentiation process upon injury remains unclear. Here, we report that during the early response of reactive gliosis, inflammation induces a conversion of mature astrocytes into neural progenitors. A TNF treatment induces the decrease of specific astrocyte markers, such as glial fibrillary acidic protein (GFAP) or genes related to glycogen metabolism, while a subset of these cells re-expresses immaturity markers, such as CD44, Musashi-1, and Oct4. Thus, TNF treatment results in the appearance of cells that exhibit a neural progenitor phenotype and are able to proliferate and differentiate into neurons and/or astrocytes. This dedifferentiation process is maintained as long as TNF is present in the culture medium. In addition, we highlight a role for Oct4 in this process, since the TNF-induced dedifferentiation can be prevented by inhibiting Oct4 expression. Our results show that activation of the NF-κB pathway through TNF plays an important role in the dedifferentiation of astrocytes via the re-expression of Oct4. These findings indicate that the first step of reactive gliosis is in fact a dedifferentiation process of resident astrocytes mediated by the NF-κB pathway.
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gabel
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg.
authors.forename: Eric
authors.initials: E
authors.lastname: Koncina
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg.
authors.forename: Gauthier
authors.initials: G
authors.lastname: Dorban
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg.
authors.forename: Tony
authors.initials: T
authors.lastname: Heurtaux
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg.
authors.forename: Cindy
authors.initials: C
authors.lastname: Birck
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, 7, avenue des Hauts-Fourneaux, Esch-Belval, G.D., L-4362, Esch-sur-Alzette, Luxembourg.
authors.forename: Enrico
authors.initials: E
authors.lastname: Glaab
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, 7, avenue des Hauts-Fourneaux, Esch-Belval, G.D., L-4362, Esch-sur-Alzette, Luxembourg.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Michelucci
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg.
authors.forename: Paul
authors.initials: P
authors.lastname: Heuschling
authors.affiliation: Life Sciences Research Unit, Faculty of Science, Technology and Communication, University of Luxembourg, Campus Limpertsberg, 162A, avenue de la Faïencerie, L-1511, Luxembourg, Luxembourg. luc.grandbarbe@uni.lu.
authors.forename: Luc
authors.initials: L
authors.lastname: Grandbarbe
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D024981:Glycogen Phosphorylase
keywords: Astrocyte; Dedifferentiation; Inflammation; NF-κB; Neural progenitor cells