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.
Spinal cord ependymal cells have stem cell properties in mice. They surround the central canal and keep expressing spinal cord developmental transcription factors. Similar cells exist in young humans however their persistence with aging is debated. We clarified this issue by collecting 17 spinal cords from organ donors, aged between 37 and 83 years old. We examined the presence of ependymal cells using immunohistochemistry on lightly-fixed tissue. We found the presence of cells expressing the typical ependymal marker FOXJ1 in the spinal cord central region in 100% of cases. In addition, a lumen surrounded by FOXJ1+ cells was observed in half of the cases. Like in mice, these human ependymal cells maintain the expression of SOX2 and PAX6 proteins together with RFX2 a master transcriptional regulator of ciliogenesis and ARL13B, a regulatory GTPase enriched in cilia. Reminiscent of the situation observed in mice and in young human spinal cord, a fetal-like regionalization of neurodevelopmental transcription factors was observed in three donors aged over 75 years: MSX1 and ARX/FOXA2 was preferentially expressed by dorsal and ventral ependymal cells, respectively. These results provide new evidence for the persistence of ependymal cells expressing neurodevelopmental genes throughout human life. The persistence of these cells in humans opens new opportunities to regenerate the spinal cord.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.