Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets
Abstract Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39059-3 |
| _version_ | 1797801364352401408 |
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| author | Zhigang Chen Yi Zhang Wenlu Li Chenyi Gao Fengbo Huang Lu Cheng Menglei Jin Xiaoming Xu Jian Huang |
| author_facet | Zhigang Chen Yi Zhang Wenlu Li Chenyi Gao Fengbo Huang Lu Cheng Menglei Jin Xiaoming Xu Jian Huang |
| author_sort | Zhigang Chen |
| collection | DOAJ |
| description | Abstract Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs. |
| first_indexed | 2024-03-13T04:49:21Z |
| format | Article |
| id | doaj.art-4d6a55bb6a704efab7be859595761da7 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T04:49:21Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4d6a55bb6a704efab7be859595761da72023-06-18T11:18:55ZengNature PortfolioNature Communications2041-17232023-06-0114111210.1038/s41467-023-39059-3Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targetsZhigang Chen0Yi Zhang1Wenlu Li2Chenyi Gao3Fengbo Huang4Lu Cheng5Menglei Jin6Xiaoming Xu7Jian Huang8Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of MedicineDepartments of Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of MedicineAbstract Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.https://doi.org/10.1038/s41467-023-39059-3 |
| spellingShingle | Zhigang Chen Yi Zhang Wenlu Li Chenyi Gao Fengbo Huang Lu Cheng Menglei Jin Xiaoming Xu Jian Huang Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets Nature Communications |
| title | Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets |
| title_full | Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets |
| title_fullStr | Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets |
| title_full_unstemmed | Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets |
| title_short | Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets |
| title_sort | single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets |
| url | https://doi.org/10.1038/s41467-023-39059-3 |
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