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PMID: 33162821 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis.

International journal of biological sciences ·Vol. 16 ·No. 16 ·2020-00-00 ·Pages 3149-3162

Pan XW, Zhang H, Xu D, Chen JX, Chen WJ, Gan SS, Qu FJ, Chu CM, Cao JW, Fan YH, Song X, Ye JQ, Zhou W, Cui XG

Abstract

Background: Cancer stem cells (CSCs) are biologically characterized by self-renewal, multi-directional differentiation and infinite proliferation, inducing anti-tumor drug resistance and metastasis. In the present study, we attempted to depict the baseline landscape of CSC-mediated biological properties, knowing that it is vital for tumor evolution, anti-tumor drug selection and drug resistance against fatal malignancy. Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis in 15208 cells from a pair of primary and metastatic sites of collecting duct renal cell carcinoma (CDRCC). Cell subpopulations were identified and characterized by t-SNE, RNA velocity, monocle and other computational methods. Statistical analysis of all single-cell sequencing data was performed in R and Python. Results: A CSC population of 1068 cells was identified and characterized, showing excellent differentiation and self-renewal properties. These CSCs positioned as a center of the differentiation process and transformed into CDRCC primary and metastatic cells in spatial and temporal order, and played a pivotal role in promoting the bone destruction process with a positive feedback loop in the bone metastasis microenvironment. In addition, CSC-specific marker genes BIRC5, PTTG1, CENPF and CDKN3 were observed to be correlated with poor prognosis of CDRCC. Finally, we pinpointed that PARP, PIGF, HDAC2, and FGFR inhibitors for effectively targeting CSCs may be the potential therapeutic strategies for CDRCC. Conclusion: The results of the present study may shed new light on the identification of CSCs, and help further understand the mechanism underlying drug resistance, differentiation and metastasis in human CDRCC.

Keywords
Cancer stem cell Cellular heterogeneity Collecting duct renal cell carcinoma Single-cell RNA sequencing Therapeutic strategy
MeSH Terms
Carcinoma, Renal Cell/genetics,pathology Cell Differentiation Drug Resistance, Neoplasm Female Humans Neoplasm Metastasis Neoplastic Stem Cells/cytology RNA-Seq Single-Cell Analysis
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Pan Xiu-Wu
Department of Urology, The Gongli Hospital of Second Military Medical University, Shanghai 200135, China. | Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Zhang Hao
Department of Bone Tumor Surgery, The Changzheng Hospital of Second Military Medical University, Shanghai 200003, China.
Xu Da
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Chen Jia-Xin
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Chen Wen-Jin
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Gan Si-Shun
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Qu Fa-Jun
Department of Urology, The Gongli Hospital of Second Military Medical University, Shanghai 200135, China.
Chu Chuan-Min
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Cao Jian-Wei
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Fan Ying-Hui
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Song Xu
Department of Urology, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
Ye Jian-Qing
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Zhou Wang
Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China. | Department of Bone Tumor Surgery, The Changzheng Hospital of Second Military Medical University, Shanghai 200003, China.
Cui Xin-Gang
Department of Urology, The Gongli Hospital of Second Military Medical University, Shanghai 200135, China. | Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai 201805, China.
Conflict of Interest

Competing Interests: The authors have declared that no competing interest exists.

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Article Info
Journal
International journal of biological sciences
Abbr.
Int J Biol Sci
ISSN
1449-2288
DOI
10.7150/ijbs.46645
Published
2020-00-00
Epub
2020-00-17
Pages
3149-3162
Language
English
Region
Australia
NLM ID
101235568
PMCID
PMC7645996
Subset
IM
External Links
PubMed source DOI: 10.7150/ijbs.46645 PMC Full Text View journal details
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