RNA Profiling of Mouse Ependymal Cells after Spinal Cord Injury Identifies the Oncostatin Pathway as a Potential Key Regulator of Spinal Cord Stem Cell Fate.

Autor: Chevreau R; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France., Ghazale H; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France., Ripoll C; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France., Chalfouh C; EA3830 GRHV, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université, UNIROUEN, 76000 Rouen, France., Delarue Q; EA3830 GRHV, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université, UNIROUEN, 76000 Rouen, France., Hemonnot-Girard AL; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France., Mamaeva D; Institut des Neurosciences de Montpellier, Université de Montpellier, INSERM, 34295 Montpellier, France., Hirbec H; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France., Rothhut B; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France., Wahane S; Departments of Neurobiology and Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA., Perrin FE; Department of Biology, University of Montpellier, INSERM MMDN, EPHE, 34295 Montpellier, France.; Institut Universitaire de France (IUF), 75231 Paris, France., Noristani HN; Shriners Hospitals Pediatric Research Center and Center for Neural Repair, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA., Guerout N; EA3830 GRHV, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université, UNIROUEN, 76000 Rouen, France., Hugnot JP; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34295 Montpellier, France.
Jazyk: angličtina
Zdroj: Cells [Cells] 2021 Nov 27; Vol. 10 (12). Date of Electronic Publication: 2021 Nov 27.
DOI: 10.3390/cells10123332
Abstrakt: Ependymal cells reside in the adult spinal cord and display stem cell properties in vitro. They proliferate after spinal cord injury and produce neurons in lower vertebrates but predominantly astrocytes in mammals. The mechanisms underlying this glial-biased differentiation remain ill-defined. We addressed this issue by generating a molecular resource through RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling post injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, seven of them more than 20-fold, namely Crym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr-the receptor for oncostatin, a microglia-specific cytokine which too is strongly upregulated after injury. We studied the regulation and role of Osmr using neurospheres derived from the adult spinal cord. We found that oncostatin induced strong Osmr and p-STAT3 expression in these cells which is associated with reduction of proliferation and promotion of astrocytic versus oligodendrocytic differentiation. Microglial cells are apposed to ependymal cells in vivo and co-culture experiments showed that these cells upregulate Osmr in neurosphere cultures. Collectively, these results support the notion that microglial cells and Osmr/Oncostatin pathway may regulate the astrocytic fate of ependymal cells in spinal cord injury.
Databáze: MEDLINE
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