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Characterization of estrogen, progesterone and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

ABSTRACT: Characterization of estrogen, progesterone and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

PROVIDER: PRJNA630686 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11711220.fastq.gz	Fastqsanger.gz
	SRR11711221.fastq.gz	Fastqsanger.gz
	SRR11711222.fastq.gz	Fastqsanger.gz
	SRR11711223.fastq.gz	Fastqsanger.gz
	SRR11711224.fastq.gz	Fastqsanger.gz

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Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization

Project description:Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization

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Characterization of estrogen, progesterone and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:The mammary epithlium goes through the drastic reorganization during development, pregnancy, and menopause as well as by external hormones and its mimicry, which risks the gland for the specific type of breast cancer. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by 17β-estradiol (E2), progesterone (P4) and polybrominated diphenyl ethers (PBDEs). Then, we integrated the transcriptomes of 50K mouse and 24K human mammary epithelial cells from five different datasets and four individuals obtained by single-cell RNA sequencing (scRNAseq). The results indicated a putative trajectory originating from the embryonic mammary stem cells and differentiating into the three different epithelial lineage (Basal, Luminal alveolar, and Luminal hormone sensing) that were presumably sustained by unipotent progenitors in the postnatal glands. The identified lineage-specific gene sets inferred cells of origin of breast cancer using The Cancer Genome Atlas data and scRNAseq of human breast cancer. The comprehensive mammary cell atlas presented novel insights into the impact of the internal and external stimulati on the mammary epithelium in an unprecedented resolution.

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Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

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Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description: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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Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland.

Project description:Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17?-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. Analysis of mammary gland RNA revealed that PBDEs both augmented E2-facilitated gene expression and modulated immune regulation. Through single-cell RNA sequencing (scRNAseq) analysis, E2 was found to induce Pgr expression in both Esr1 + and Esr1 - luminal epithelial cells and Ccl2 expression in Esr1 + fibroblasts. PBDEs promote the E2-AREG-EGFR-M2 macrophage pathway. Our findings support that E2?+?PBDE increases the risk of developing breast cancer through the expansion of estrogen-responsive luminal epithelial cells and immune modulation.

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