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Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing
Sun, Heng1,2,3,4; Zeng, Jianming1,2; Miao, Zhengqiang1,2; Lei, Kuan Cheok1,2; Huang, Chen1,2; Hu, Lingling1,2; Su, Sek Man1,2; Chan, Un In1,2; Miao, Kai1,2,3; Zhang, Xu1,2; Zhang, Aiping1,2; Guo, Sen1,2; Chen, Si1,2; Meng, Ya1,2,5; Deng, Min1,2; Hao, Wenhui1,2; Lei, Haipeng1,2; Lin, Ying6; Yang, Zhonglin7,8,9,10; Tang, Dongjiang7,8,9,10; Wong, Koon Ho1,2; Zhang, Xiaohua Douglas1,2,3; Xu, Xiaoling1,2,3; Deng, Chu Xia1,2,3
2021
Source PublicationTheranostics
Volume11Issue:20Pages:9967-9987
AbstractBackground: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.
KeywordBrca1/BRCA1 Mammary tumor Mrc2 Single cell RNA-seq Tumor heterogeneity
DOI10.7150/THNO.63995
URLView the original
Language英語English
Scopus ID2-s2.0-85119377160
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Cancer Center, Faculty of Health Sciences, University of Macau, Macao
2.Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macao
3.MOE Frontiers Science Center for Precision Oncology, University of Macau, Macao
4.Zhuhai Research Institute, University of Macau, Macao
5.Zhuhai Precision Medical Center, Zhuhai People's Hospital, Jinan University, Zhuhai, China
6.Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
7.Zhuhai SanMed Biotech Ltd, Zhuhai, China
8.Joint Research Center of Liquid Biopsy in Guangdong, Hong Kong
9.Joint Research Center of Liquid Biopsy in Guangdong, Macao
10.Joint Research Center of Liquid Biopsy in Guangdong, Zhuhai, China
First Author AffilicationCancer Centre;  Faculty of Health Sciences;  University of Macau
Recommended Citation
GB/T 7714
Sun, Heng,Zeng, Jianming,Miao, Zhengqiang,et al. Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing[J]. Theranostics,2021,11(20):9967-9987.
APA Sun, Heng.,Zeng, Jianming.,Miao, Zhengqiang.,Lei, Kuan Cheok.,Huang, Chen.,Hu, Lingling.,Su, Sek Man.,Chan, Un In.,Miao, Kai.,Zhang, Xu.,Zhang, Aiping.,Guo, Sen.,Chen, Si.,Meng, Ya.,Deng, Min.,Hao, Wenhui.,Lei, Haipeng.,Lin, Ying.,Yang, Zhonglin.,...&Deng, Chu Xia.(2021).Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing.Theranostics,11(20),9967-9987.
MLA Sun, Heng,et al."Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing".Theranostics 11.20(2021):9967-9987.
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