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Single-cell sequencing reveals variants driving self-renewal of human bladder cancer stem cells

Author: Update time: 2016-11-14

Drs. Chong Li, Zhao Yang and Song Wu published online two papers in the European Urology. (1)Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells.; (2)Reply from Authors re: Xue-Ru Wu. Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells.The authors reveal the origin of human bladder cancer stem cells by Single-cell sequencing. This is the first study to ever report such an association.

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.

(1) Yang Z#, Li C#, Liu H, Zhang X, Cai Z, Xu L, Luo J, Huang Y, He L, Liu C, Wu S*. Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells. Eur Urol. http://dx.doi.org/10.1016/j.eururo.2016.06.025. (IF=14.976) 

(2) Yang Z*, Wu S, Cai Z, Li C*. Reply from Authors re: Xue-Ru Wu. Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells. Eur Urol. http://dx.doi.org/10.1016/j.eururo.2016.11.003. (IF=14.976) 

 

Figure. 1 Single-cell sequencing and phylogenetic analysis of bladder cancer cells. (A) The neighbor joining phylogenetic tree is constructed by Euclidean distance. (B) Key genes with somatic mutation. (C) The relative frequency each somatic mutation in single cells. (Image by IBP)

Contact:

LI Chong

Associate Professor

Tel: 86-10-64888424

Email: lichong@moon.ibp.ac.cn

 

 

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