Abstract
Spinal cord injury (SCI) induced catastrophic neurological disability is often incurable at present. The injury triggered immediately oligodendrocytes loss and overwhelming demyelination are regarded as an insurmountable barrier to SCI recovery. To date, effective strategy to promote the endogenous oligodendrocytes replacement post SCI remains elusive. Epigenetic modifications are emerging as critical molecular switches of gene expression in CNS. However, the epigenetic mechanisms underlying oligodendrogenesis post SCI yet to be discovered. In this study, we report that H3K27me3 demethylase JMJD3 exists as a pivotal epigenetic regulator which manipulates the endogenous oligodendrogenesis post SCI. We found that JMJD3 inhibition promotes the oligodendrocyte linage commitment of neural stem/progenitor cells (NPCs) in vitro and in vivo. Moreover, we demonstrated that JMJD3 inhibition mediated SAPK/JNK signaling inactivation is functionally necessary for endogenous oligodendrocyte-lineage commitment post SCI. Our results also suggested that JMJD3 is downstream of SAPK/JNK pathway, and capable of translates SCI induced SAPK/JNK signaling into epigenetic codes readable by spinal cord endogenous NPCs. Taken together, our findings provide novel evidence of JMJD3 mediated oligodendrocyte-lineage commitment orchestration post SCI, which would be a potential epigenetic approach to induce the mature mammalian endogenous recovery.
Highlights
Spinal cord injury (SCI) is a catastrophic neurotraumatic event which results in permanent neurological disability
The present study, we reported that H3K27me3 demethylase JMJD3 regulates the oligodendrogenesis post SCI
The injury induced OLs loss and demyelination occurred immediately post SCI, which disrupt the neural circuits destructively [28]. (Fig. S6) effective interventions to promote the spontaneous OLs replacement will be bound to cross the intrinsic barrier to SCI recovery [10, 29]
Summary
Spinal cord injury (SCI) is a catastrophic neurotraumatic event which results in permanent neurological disability. With the development of transportation and construction in recent years, the incidence rate of SCI elevated progressively. It is estimated that the worldwide annual arising of new SCI cases is more than 760,000 approximately. SCI triggered devastating neurological symptoms is still incurable [2]. Oligodendrocytes (OLs) orchestrate the axon myelin sheaths in central nervous system (CNS), which guarantee the neural signal rapid transmission and axon metabolic support [3]. OLs are extremely vulnerable to the SCI strike [4]. Primary neurotrauma usually triggers serious OLs loss and diffused demyelination immediately, which impairs the axon conduction capacity and survival eventually [5, 6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
