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单细胞测序鉴定到髓母细胞瘤的前体细胞
作者:小柯机器人 发布时间:2019/8/30 14:03:50

美国辛辛那提儿童医院医疗中心Q. Richard Lu和Xuelian He等研究人员合作利用髓母细胞瘤单细胞转录组学,发现肿瘤发生与复发时起始的前体细胞以及致癌级联信号。该项研究成果2019年8月29日在线发表在《癌细胞》上。

利用单细胞转录组学分析,研究人员证明了SHH(Sonic Hedgehog)髓母细胞瘤中前体细胞群的发育层次,并且鉴定了表达OLIG2的神经胶质前体细胞在肿瘤发生时作为转移-扩增细胞。尽管OLIG2阳性前体细胞在完整的肿瘤中成为静止的干细胞样细胞,但它们在治疗抗性和复发性髓母细胞瘤中高度富集。去除分裂的Olig2阳性前体细胞或Olig2的敲除能够阻碍肿瘤的发生。基因组分析显示OLIG2调节染色质形貌并激活致癌网络,包括HIPPO-YAP /TAZ和AURORA-A/MYCN途径。共同靶向这些致癌途径能够导致肿瘤生长停滞。总之,这些结果表明胶质细胞谱系相关的OLIG2 阳性前体细胞是髓母细胞瘤发生和复发期间的肿瘤起始细胞,并表明OLIG2驱动的致癌网络是潜在的治疗靶标。

据悉,在髓母细胞瘤中肿瘤起始和复发的前体细胞异质性和身份仍然是难以捉摸的。

附:英文原文

Title: Single-Cell Transcriptomics in Medulloblastoma Reveals Tumor-Initiating Progenitors and Oncogenic Cascades during Tumorigenesis and Relapse

Author: Liguo Zhang, Xuelian He, Xuezhao Liu, Feng Zhang, L. Frank Huang, Andrew S. Potter, Lingli Xu, Wenhao Zhou, Tao Zheng, Zaili Luo, Kalen P. Berry, Allison Pribnow, Stephanie M. Smith, Christine Fuller, Blaise V. Jones, Maryam Fouladi, Rachid Drissi, Zeng-Jie Yang, W. Clay Gustafson, Marc Remke, Scott L. Pomeroy, Emily J. Girard, James M. Olson, A. Sorana Morrissy, Maria C. Vladoiu, Jiao Zhang, Weidong Tian, Mei Xin, Michael D. Taylor, S. Steven Potter, Martine F. Roussel, William A. Weiss, Q. Richard Lu

Issue&Volume: 29 August 2019

Abstract: Progenitor heterogeneity and identities underlying tumor initiation and relapse in medulloblastomas remain elusive. Utilizing single-cell transcriptomic analysis, we demonstrated a developmental hierarchy of progenitor pools in Sonic Hedgehog (SHH) medulloblastomas, and identified OLIG2-expressing glial progenitors as transit-amplifying cells at the tumorigenic onset. Although OLIG2 + progenitors become quiescent stem-like cells in full-blown tumors, they are highly enriched in therapy-resistant and recurrent medulloblastomas. Depletion of mitotic Olig2 + progenitors or Olig2 ablation impeded tumor initiation. Genomic profiling revealed that OLIG2 modulates chromatin landscapes and activates oncogenic networks including HIPPO-YAP/TAZ and AURORA-A/MYCN pathways. Co-targeting these oncogenic pathways induced tumor growth arrest. Together, our results indicate that glial lineage-associated OLIG2 + progenitors are tumor-initiating cells during medulloblastoma tumorigenesis and relapse, suggesting OLIG2-driven oncogenic networks as potential therapeutic targets.

DOI: https://doi.org/10.1016/j.ccell.2019.07.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30336-8#

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx