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Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing
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 o...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581428/ https://www.ncbi.nlm.nih.gov/pubmed/34815798 http://dx.doi.org/10.7150/thno.63995 |
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author | 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 Tang, Dongjiang Wong, Koon Ho Zhang, Xiaohua Douglas Xu, Xiaoling Deng, Chu-Xia |
author_facet | 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 Tang, Dongjiang Wong, Koon Ho Zhang, Xiaohua Douglas Xu, Xiaoling Deng, Chu-Xia |
author_sort | Sun, Heng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8581428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-85814282021-11-22 Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing 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 Tang, Dongjiang Wong, Koon Ho Zhang, Xiaohua Douglas Xu, Xiaoling Deng, Chu-Xia Theranostics Research Paper 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. Ivyspring International Publisher 2021-10-25 /pmc/articles/PMC8581428/ /pubmed/34815798 http://dx.doi.org/10.7150/thno.63995 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper 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 Tang, Dongjiang Wong, Koon Ho Zhang, Xiaohua Douglas Xu, Xiaoling Deng, Chu-Xia Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing |
title | Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing |
title_full | Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing |
title_fullStr | Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing |
title_full_unstemmed | Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing |
title_short | Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing |
title_sort | dissecting the heterogeneity and tumorigenesis of brca1 deficient mammary tumors via single cell rna sequencing |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581428/ https://www.ncbi.nlm.nih.gov/pubmed/34815798 http://dx.doi.org/10.7150/thno.63995 |
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