我们在《欧洲泌尿学》杂志上发表文章：ARID1A, GPRC5A与MLL2 变异驱动膀胱癌干细胞自我更新的研究
Eur Urol. 2017 Jan;71(1):8-12. doi: 10.1016/j.eururo.2016.06.025. Epub 2016 Jul 4.
Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells.
Yang Z, Li C, Fan Z, Liu H, Zhang X, Cai Z, Xu L, Luo J, Huang Y, He L, Liu C, Wu S.
Cancer stem cells are considered responsible for many important aspects of tumors such as their self-renewal, tumor-initiating, drug-resistance and metastasis. However, the genetic basis and origination of human bladder cancer stem cells (BCSCs) remains unknown. Here, we conducted single-cell sequencing on 59 cells including BCSCs, bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. Moreover, 21 key altered genes were identified in BCSCs including six genes not previously described in BC (ETS1, GPRC5A, MKL1, PAWR, PITX2 and RGS9BP). Co-mutations of ARID1A, GPRC5A and MLL2 introduced by CRISPR/Cas9 significantly enhance the capabilities of self-renewal and tumor-initiating of BCNSCs. To our knowledge, our study first provides an overview of the genetic basis of human BCSCs with single-cell sequencing and demonstrates the biclonal origin of human BCSCs via evolution analysis.
Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self-renewal.
Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
bladder cancer; bladder cancer stem cells; genetic alteration; self-renewal; single-cell sequencing; tumor evolution
Attention to Detail by Single-cell Sequencing. [Eur Urol. 2017]
Reply from Authors re: Xue-Ru Wu. Attention to Detail by Single-cell sequencing. Eur Urol 2017;71:13-4. [Eur Urol. 2017]
PMID: 27387124 DOI: 10.1016/j.eururo.2016.06.025