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摘要 : 2016年11月2日,国际学术权威刊物自然出版集团《Nature》杂志在线发表了麻省总院Broad研究所Mario Suvà研究员的一篇研究论文,研究在单细胞水平上对脑瘤进行基因组分析,在人类脑瘤样本中鉴定到了癌症干细胞及其分化后代。

 2016年11月2日,国际学术权威刊物自然出版集团《Nature》杂志在线发表了麻省总院Broad研究所Mario Suvà研究员的一篇研究论文,研究在单细胞水平上对脑瘤进行基因组分析,在人类脑瘤样本中鉴定到了癌症干细胞及其分化后代。

少突胶质细胞瘤是一种生长缓慢但无法治愈的脑瘤。“我们提出了强有力的证据,证明癌症干细胞是少突胶质细胞瘤的主要生长源,这些细胞将成为很有前景的治疗靶标,”Mario Suvà说。为了准确分析少突胶质细胞瘤,研究人员在单细胞水平上进行了RNA测序研究。



Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma


Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny1. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, wheras a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.

来源: Nature 浏览次数:0


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