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| Status |
Public on Nov 12, 2019 |
| Title |
Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Exposure to estrogen and its mimics during menopausal transition is thought to modify the structure of mammary gland. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). Three analyzed flame retardants, BDE-47, BDE-100 and BDE-153, are most frequently detected in human serum from all over the world. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. According to sequencing analysis of mammary gland RNA, PBDEs both augmented E2-facilitated cell proliferationgene expression changes and modulated immune regulation. To better elucidate the effects of E2 and PBDEs, single-cell RNA sequencing (scRNAseq) analysis was performed. In a definitive manner, E2 was found to induce Pgr expression in both Esr1+ and Esr1- cells. Significantly, molecular evidence was available to show functional differences among cells with differential expression of Esr1 and Pgr. The PBDEs + E2 treatment increased the number of double positive (Esr1+Pgr+) and Pgr only (Esr1-Pgr+) cells in both mature luminal epithelial and progenitor cells of luminal epithelialcells. Moreover, the combination increased the mammary gland population of M2 macrophages. The results help clarify how exposure to both E2 and endocrine disrupting chemicals like PBDEs during menopausal transition impact mammary gland structure. Ultimately, the findings advance understanding of how exposure can increase the risk of developing breast cancer.
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| Overall design |
Female BALB/cj mice were exposed to E2 and a mixture of PBDEs for 1 week. Single-cell RNA sequencing was done to evaluate gene expression changes among treatment groups. Mice were subjected to 3 different treatments (Vehicle, E2, E2+PBDE).
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| Contributor(s) |
Shiuan C, Kanaya N |
| Citation(s) |
31701034 |
| |
| Submission date |
Jan 17, 2019 |
| Last update date |
Mar 24, 2023 |
| Contact name |
Xiwei Wu |
| E-mail(s) |
xwu@coh.org
|
| Organization name |
City of Hope National Medical Center
|
| Department |
Computational and Quantitative Medicine
|
| Street address |
1500 E. Duarte Rd.
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE228190 |
Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization |
|
| Relations |
| BioProject |
PRJNA515727 |
| SRA |
SRP180002 |
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