CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas.

BACKGROUND: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies. METHODS: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGGINV) and tumor core (HGGTC) cells. RESULTS: pHGGINV cells were intrinsically more invasive than their matching pHGGTC cells. CSC profiling revealed co-positivity of CD133 and CD57 and identified CD57+CD133- cells as the most abundant CSCs in the invasive front. In addition to discovering a new order of self-renewal capacities, i.e., CD57+CD133- > CD57+CD133+ > CD57-CD133+ > CD57-CD133- cells, we showed that CSC hierarchy was impacted by their spatial locations, and the highest self-renewal capacities were found in CD57+CD133- cells in the HGGINV front (HGGINV/CD57+CD133- cells) mediated by NANOG and SHH over-expression. Direct implantation of CD57+ (CD57+/CD133- and CD57+/CD133+) cells into mouse brains reconstituted diffusely invasion, while depleting CD57+ cells (i.e., CD57-CD133+) abrogated pHGG invasion. CONCLUSION: We revealed significantly increased invasive capacities in HGGINV cells, confirmed CD57 as a novel glioma stem cell marker, identified CD57+CD133- and CD57+CD133+ cells as a new cellular driver of pHGG invasion and suggested a new dual-mode hierarchy of HGG stem cells.

Slo2 potassium channel function depends on RNA editing-regulated expression of a SCYL1 protein.

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans may cause epilepsies and cognitive defects. However, it is largely unknown how Slo2 is regulated by other proteins. Here we show that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editing. ADR-1 promotes SLO-2 function not by editing the transcripts of slo-2 but those of scyl-1, which encodes an orthologue of mammalian SCYL1. Transcripts of scyl-1 are greatly decreased in adr-1 mutants due to deficient RNA editing at a single adenosine in their 3'-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability (Po) of neuronal SLO-2 is ~50% lower in scyl-1 knockout mutant than wild type. Moreover, human Slo2.2/Slack Po is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.

Chromatin Architectures Are Associated with Response to Dark Treatment in the Oil Crop Sesamum indicum, Based on a High-Quality Genome Assembly.

Eukaryotic chromatin is tightly packed into hierarchical structures, allowing appropriate gene transcription in response to environmental and developmental cues. Here, we provide a chromosome-scale de novo genome assembly of sesame with a total length of 292.3 Mb and a scaffold N50 of 20.5 Mb, containing estimated 28,406 coding genes using Pacific Biosciences long reads combined with a genome-wide chromosome conformation capture (Hi-C) approach. Based on this high-quality reference genome, we detected changes in chromatin architectures between normal growth and dark-treated sesame seedlings. Gene expression level was significantly higher in 'A' compartment and topologically associated domain (TAD) boundary regions than in 'B' compartment and TAD interior regions, which is coincident with the enrichment of H4K3me3 modification in these regions. Moreover, differentially expressed genes (DEGs) induced by dark treated were enriched in the changed TAD-related regions and genomic differential contact regions. Gene Ontology (GO) enrichment analysis of DEGs showed that genes related to 'response to stress' and 'photosynthesis' functional categories were enriched, which corresponds to dark treatment. These results suggested that chromatin organization is associated with gene transcription in response to dark treatment in sesame. Our results will facilitate the understanding of regulatory mechanisms in response to environmental cues in plants.

Glioblastoma: Targeting the autophagy in tumorigenesis.

Glioblastoma (GBM) is one of the most malignant and aggressive primary brain tumor, with a mean life expectancy of less than 15 months. The malignant nature of GBM prompts the need for further research on its tumorigenesis and novel treatments to improve its outcome. One of the promising research targets is autophagy, a fundamental metabolic process of degrading and recycling cellular components. Interventions to activate or inhibit autophagy have both been proposed as GBM therapies, suggesting a controversial, context-dependent role of autophagy in GBM tumorigenesis. In this review, we highlight the molecular links between GBM and autophagy with the focus on the effects of autophagy on the stemness maintenance, metabolism and proteostasis in GBM tumorigenesis. Understanding the molecular pathways involved in autophagy target is critical for GBM therapy.