UM  > Faculty of Health Sciences  > DEPARTMENT OF BIOMEDICAL SCIENCES
Residential Collegefalse
Status已發表Published
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
ISSN1838-7640
Volume11Issue:20Pages:9967 - 9987
Abstract

Background: 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
Indexed BySCIE
Language英語English
WOS Research AreaResearch & Experimental Medicine
WOS SubjectMedicine, Research & Experimental
WOS IDWOS:000719124500002
PublisherIVYSPRING INT PUBL, PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
Scopus ID2-s2.0-85119377160
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Faculty of Health Sciences
Cancer Centre
Centre for Precision Medicine Research and Training
Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau
Corresponding AuthorDeng, Chu Xia
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
Corresponding 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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Sun, Heng]'s Articles
[Zeng, Jianming]'s Articles
[Miao, Zhengqiang]'s Articles
Baidu academic
Similar articles in Baidu academic
[Sun, Heng]'s Articles
[Zeng, Jianming]'s Articles
[Miao, Zhengqiang]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Sun, Heng]'s Articles
[Zeng, Jianming]'s Articles
[Miao, Zhengqiang]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.