ABSTRACT
Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Subject(s)
Mice , Animals , Humans , Glioblastoma/pathology , Endothelial Cells/pathology , DNA Copy Number Variations , Brain/metabolism , Brain Neoplasms/pathologyABSTRACT
Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.
ABSTRACT
Contrast-enhanced CT is a conventional imaging technique for assessing the effect of TACE for treating hepatocellular carcinoma (HCC). Recent years, with the continuous advances of technology and equipment, ultrasound has become more and more important in the diagnosis and therapeutic evaluation of HCC, which have the advantages of safety, convenience and low price. The advancements of ultrasound in therapeutic evaluation of HCC treated with TACE were reviewed in this article.
ABSTRACT
Objective:To investigate the effect of continuous use of aspirin on gallbladder function and thromboembolism risk in the patients undergoing laparoscopic cholecystectomy. Methods:Totally 100 patients undergoing laparoscopic cholecystectomy from October 2010 to October 2014 were selected as the subjects. All the patients were given aspirin for a long time and randomly divided into two groups. The patients in the observation group were treated with aspirin continuously, and the control group suspended aspirin 7 days before the surgery and administrated aspirin continuously after the surgery. The perioperative thromboembolism,changes in gallbladder function and coagulation function, and intraoperative and postoperative differences in the indicators were compared between the groups. Results:The gallbladder volume in the observation group decreased, and the gallbladder contraction rate and emptying index were higher than those on the 7th day before the surgery(P < 0.05). The above indices were significantly better than those in the control group (P < 0.05). There was no significant change in the coagulation function after the treatment in both groups(P >0.05). There were no significant differences in the operative time,intraoperative blood loss, postoperative drainage and postoperative hospital stay between the groups (P > 0.05). The total incidence of perioperative thromboembolism in the observation group was 2.0%,which was significantly lower than that in the control group(P< 0.05).Conclusion:Continuous use of aspirin during laparoscopic cholecystectomy is beneficial to reducing the volume of gallbladder, promoting gallbladder emptying and reducing the risk of perioperative thromboembolism. The reasonable use has no obvious effect on the postoperative coagulation function.