Background5-methylcytosine (mC) can be oxidized by the tet methylcytosine dioxygenase (Tet) family of enzymes to 5-hydroxymethylcytosine (hmC), which is an intermediate of mC demethylation and may also be a stable epigenetic modification that influences chromatin structure. hmC is particularly abundant in mammalian brains but its function is currently unknown. A high-resolution hydroxymethylome map is required to fully understand the function of hmC in the human brain.ResultsWe present genome-wide and single-base resolution maps of hmC and mC in the human brain by combined application of Tet-assisted bisulfite sequencing and bisulfite sequencing. We demonstrate that hmCs increase markedly from the fetal to the adult stage, and in the adult brain, 13% of all CpGs are highly hydroxymethylated with strong enrichment at genic regions and distal regulatory elements. Notably, hmC peaks are identified at the 5′splicing sites at the exon-intron boundary, suggesting a mechanistic link between hmC and splicing. We report a surprising transcription-correlated hmC bias toward the sense strand and an mC bias toward the antisense strand of gene bodies. Furthermore, hmC is negatively correlated with H3K27me3-marked and H3K9me3-marked repressive genomic regions, and is more enriched at poised enhancers than active enhancers.ConclusionsWe provide single-base resolution hmC and mC maps in the human brain and our data imply novel roles of hmC in regulating splicing and gene expression. Hydroxymethylation is the main modification status for a large portion of CpGs situated at poised enhancers and actively transcribed regions, suggesting its roles in epigenetic tuning at these regions.

Increasing evidence has indicated that the disorganized expression of certain genes promotes tumour progression. In this study, we elucidate the potential key differentially expressed genes (DEGs) between glioblastoma (GBM) and normal brain tissue by analysing three different mRNA expression profiles downloaded from the Gene Expression Omnibus (GEO) database. DEGs were sorted, and key candidate genes and signalling pathway enrichments were analysed. In our analysis, the highest fold change DEG was found to be abnormal spindle-like microcephaly associated (ASPM). The ASPM expression pattern from the database showed that it is highly expressed in GBM tissue, and patients with high expression of ASPM have a poor prognosis. Moreover, ASPM showed aberrantly high expression in GBM cell lines. Loss-of-function assay indicated that ASPM enhances tumorigenesis in GBM cells in vitro. Xenograft growth verified the oncogenic activity of ASPM in vivo. Furthermore, downregulation of ASPM could arrest the cell cycle of GBM cells at the G0/G1 phase and attenuate the Wnt/β-catenin signalling activity in GBM. These data suggest that ASPM may serve as a new target for the therapeutic treatment of GBM.

BackgroundIdiopathic spinal cord herniation is an extremely rare entity that is characterized by protrusion of the spinal cord through a defect in the ventral dura. Due to the paucity of enough clinical evidence, the treatment and prognosis of idiopathic spinal cord herniation are still elusive. Herein, we reported a case of idiopathic spinal cord herniation occurring at the C7–T1 levels that was treated by surgical reduction.Case descriptionA 44-year-old Chinese woman presented with a 5-year history of numbness and weakness in the bilateral lower limbs. Spinal magnetic resonance imaging demonstrated ventral displacement of the spinal cord at the C7–T1 levels, and there seemed to be a cuneiform space-occupying lesion dorsal to the spinal cord. A diagnosis of the spinal intradural extramedullary tumor was suspected. An exploratory operation was performed via a posterior midline approach. Intraoperatively, we found a defect in the ventral dura through which the spinal cord herniated to the epidural space. After the herniated parenchyma was returned, an artificial dura matter was used to repair the defect. The postoperative course was uneventful. After a 3-month follow-up, the lower-extremity weakness was significantly improved, and there was no recurrence of the spinal cord herniation.ConclusionPreoperative diagnosis of idiopathic spinal cord herniation is exceedingly challenging. Surgical reduction of the herniated spinal cord with the repair of the dural defect is an effective approach for the treatment of this rare disorder, and the surgical outcome is favorable.

No abstract