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: | Florence E. Perrin, Jean-Philippe Hugnot, Shalaka Wahane, Quentin Delarue, Nicolas Guérout, Harun N. Noristani, Bernard Rothhut, Hélène Hirbec, Robert Chevreau, Hussein Ghazale, Chantal Ripoll, Anne Laure Hemonnot-Girard, Daria Mamaeva, Chaima Chalfouh |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Ependymal Cell
injury QH301-705.5 Down-Regulation microglia Oncostatin M Biology Article Mice stem cells spinal cord regeneration ependyma oncostatin Spheroids Cellular Neurosphere Ciliogenesis medicine Animals Cell Lineage Cilia Biology (General) Spinal cord injury Spinal Cord Injuries Cell Proliferation Oncostatin M Receptor beta Subunit Microglia Gene Expression Profiling Cell Differentiation General Medicine Spinal cord medicine.disease Up-Regulation Cell biology Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Intercellular Signaling Peptides and Proteins RNA Stem cell Ependyma |
Zdroj: | Cells; Volume 10; Issue 12; Pages: 3332 Cells, Vol 10, Iss 3332, p 3332 (2021) Cells |
ISSN: | 2073-4409 |
DOI: | 10.3390/cells10123332 |
Popis: | 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: | OpenAIRE |
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