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

Author:

Chevreau Robert,Ghazale Hussein,Ripoll Chantal,Chalfouh Chaima,Delarue Quentin,Hemonnot-Girard Anne LaureORCID,Mamaeva Daria,Hirbec HeleneORCID,Rothhut Bernard,Wahane Shalaka,Perrin Florence EvelyneORCID,Noristani Harun NajibORCID,Guerout NicolasORCID,Hugnot Jean Philippe

Abstract

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.

Funder

Institut pour la Recherche sur la Moelle épinière et l’Encéphale

French Muscular Dystrophy Association

International Foundation for Research in Paraplegia

Association Nationale de la Recherche et de la Technologie

Publisher

MDPI AG

Subject

General Medicine

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