Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland
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 17β-estradiol (E2) and polybrominated diphen...
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| Veröffentlicht in: | Communications biology 2019-11, Vol.2 (1), p.406, Article 406 |
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| creator | Kanaya, Noriko Chang, Gregory Wu, Xiwei Saeki, Kohei Bernal, Lauren Shim, Hyun-Jeong Wang, Jinhui Warden, Charles Yamamoto, Takuro Li, Jay Park, June-Soo Synold, Timothy Vonderfecht, Steve Rakoff, Michele Neuhausen, Susan L. Chen, Shiuan |
| 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 17β-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.
Kanaya et al. show that endocrine-disrupting chemicals polybrominated diphenyl ethers (PBDEs) enhance 17β-estradiol-mediated regrowth of mammary glands. This study suggests that PBDE may increase the risk of developing breast cancer by regulating the growth of estrogen-responsive luminal epithelial cells and the immune response. |
| doi_str_mv | 10.1038/s42003-019-0618-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6831695</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2389680364</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-1e3ea419998f75a6f7a8e681493bf7c4c0a2d4d7020ecde07b5b48eb8fe398a03</originalsourceid><addsrcrecordid>eNp1kU1LHTEUhkOpVNH7A7opA65jk0luJtkIIq0tXFrwYx0yyZkxMpNckxnBrvzpZrjW6qKrhHPe85yPF6HPlJxQwuTXzGtCGCZUYSKoxOoDOqiZUpgJXn98899Hq5zvCClKpQTjn9A-ow0pEH6Anq586AfAFoahuvx1hjPczxBsiVYmmOEx-1zFroI8pdhDwCXqKggu2uQDYOdzmrfTIre3MHprBuyDmy24KkFMvQn-j5l8DAtljHOGajTjaNJj1Q-FdYT2OjNkWL28h-jm-7fr8x948_vi5_nZBts1ExOmwMDwZQPZNWsjusZIEJJyxdqusdwSUzvuGlITsA5I065bLqGVHTAlDWGH6HTH3c7tCM5CmJIZ9Db5ZRYdjdfvM8Hf6j4-aCEZFWpdAMcvgBTLifKk7-KcyomyrplUQpJy7KKiO5VNMecE3WsHSvTim975posbevFNq1Lz5e1orxV_XSqCeifIJRV6SP9a_5_6DNMfpr8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2389680364</pqid></control><display><type>article</type><title>Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><source>PubMed Central Open Access</source><creator>Kanaya, Noriko ; Chang, Gregory ; Wu, Xiwei ; Saeki, Kohei ; Bernal, Lauren ; Shim, Hyun-Jeong ; Wang, Jinhui ; Warden, Charles ; Yamamoto, Takuro ; Li, Jay ; Park, June-Soo ; Synold, Timothy ; Vonderfecht, Steve ; Rakoff, Michele ; Neuhausen, Susan L. ; Chen, Shiuan</creator><creatorcontrib>Kanaya, Noriko ; Chang, Gregory ; Wu, Xiwei ; Saeki, Kohei ; Bernal, Lauren ; Shim, Hyun-Jeong ; Wang, Jinhui ; Warden, Charles ; Yamamoto, Takuro ; Li, Jay ; Park, June-Soo ; Synold, Timothy ; Vonderfecht, Steve ; Rakoff, Michele ; Neuhausen, Susan L. ; Chen, Shiuan</creatorcontrib><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 17β-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.
Kanaya et al. show that endocrine-disrupting chemicals polybrominated diphenyl ethers (PBDEs) enhance 17β-estradiol-mediated regrowth of mammary glands. This study suggests that PBDE may increase the risk of developing breast cancer by regulating the growth of estrogen-responsive luminal epithelial cells and the immune response.</description><identifier>ISSN: 2399-3642</identifier><identifier>EISSN: 2399-3642</identifier><identifier>DOI: 10.1038/s42003-019-0618-9</identifier><identifier>PMID: 31701034</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 17β-Estradiol ; 38/91 ; 631/114 ; 631/67/1347 ; 64/60 ; 692/163 ; 82/51 ; Animals ; Biology ; Biomedical and Life Sciences ; Breast cancer ; Endocrine disruptors ; Endocrine Disruptors - toxicity ; Epidermal growth factor receptors ; Epithelial cells ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Estradiol - toxicity ; Estrogen Receptor alpha - metabolism ; Estrogen receptors ; Ethers ; Female ; Fibroblasts ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Flame retardants ; Flame Retardants - toxicity ; Gene expression ; Gene Expression Profiling ; Halogenated Diphenyl Ethers - toxicity ; Household products ; Humans ; Immune response ; Immunomodulation ; Immunoregulation ; Life Sciences ; Macrophages ; Mammary gland ; Mammary Glands, Animal - drug effects ; Mammary Glands, Animal - metabolism ; Mammary Glands, Animal - pathology ; Menopause ; Mice ; Mice, Inbred BALB C ; Monocyte chemoattractant protein 1 ; Ovariectomy ; Polybrominated diphenyl ethers ; Receptors, Progesterone - metabolism ; Ribonucleic acid ; RNA ; RNA-Seq ; Sequence analysis ; Single-Cell Analysis</subject><ispartof>Communications biology, 2019-11, Vol.2 (1), p.406, Article 406</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019.</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-1e3ea419998f75a6f7a8e681493bf7c4c0a2d4d7020ecde07b5b48eb8fe398a03</citedby><cites>FETCH-LOGICAL-c536t-1e3ea419998f75a6f7a8e681493bf7c4c0a2d4d7020ecde07b5b48eb8fe398a03</cites><orcidid>0000-0002-1827-4486 ; 0000-0002-4482-6926</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831695/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831695/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31701034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kanaya, Noriko</creatorcontrib><creatorcontrib>Chang, Gregory</creatorcontrib><creatorcontrib>Wu, Xiwei</creatorcontrib><creatorcontrib>Saeki, Kohei</creatorcontrib><creatorcontrib>Bernal, Lauren</creatorcontrib><creatorcontrib>Shim, Hyun-Jeong</creatorcontrib><creatorcontrib>Wang, Jinhui</creatorcontrib><creatorcontrib>Warden, Charles</creatorcontrib><creatorcontrib>Yamamoto, Takuro</creatorcontrib><creatorcontrib>Li, Jay</creatorcontrib><creatorcontrib>Park, June-Soo</creatorcontrib><creatorcontrib>Synold, Timothy</creatorcontrib><creatorcontrib>Vonderfecht, Steve</creatorcontrib><creatorcontrib>Rakoff, Michele</creatorcontrib><creatorcontrib>Neuhausen, Susan L.</creatorcontrib><creatorcontrib>Chen, Shiuan</creatorcontrib><title>Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland</title><title>Communications biology</title><addtitle>Commun Biol</addtitle><addtitle>Commun Biol</addtitle><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 17β-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.
Kanaya et al. show that endocrine-disrupting chemicals polybrominated diphenyl ethers (PBDEs) enhance 17β-estradiol-mediated regrowth of mammary glands. This study suggests that PBDE may increase the risk of developing breast cancer by regulating the growth of estrogen-responsive luminal epithelial cells and the immune response.</description><subject>13/1</subject><subject>17β-Estradiol</subject><subject>38/91</subject><subject>631/114</subject><subject>631/67/1347</subject><subject>64/60</subject><subject>692/163</subject><subject>82/51</subject><subject>Animals</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Endocrine disruptors</subject><subject>Endocrine Disruptors - toxicity</subject><subject>Epidermal growth factor receptors</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Estradiol - toxicity</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen receptors</subject><subject>Ethers</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Flame retardants</subject><subject>Flame Retardants - toxicity</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Halogenated Diphenyl Ethers - toxicity</subject><subject>Household products</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Life Sciences</subject><subject>Macrophages</subject><subject>Mammary gland</subject><subject>Mammary Glands, Animal - drug effects</subject><subject>Mammary Glands, Animal - metabolism</subject><subject>Mammary Glands, Animal - pathology</subject><subject>Menopause</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Ovariectomy</subject><subject>Polybrominated diphenyl ethers</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA-Seq</subject><subject>Sequence analysis</subject><subject>Single-Cell Analysis</subject><issn>2399-3642</issn><issn>2399-3642</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1LHTEUhkOpVNH7A7opA65jk0luJtkIIq0tXFrwYx0yyZkxMpNckxnBrvzpZrjW6qKrhHPe85yPF6HPlJxQwuTXzGtCGCZUYSKoxOoDOqiZUpgJXn98899Hq5zvCClKpQTjn9A-ow0pEH6Anq586AfAFoahuvx1hjPczxBsiVYmmOEx-1zFroI8pdhDwCXqKggu2uQDYOdzmrfTIre3MHprBuyDmy24KkFMvQn-j5l8DAtljHOGajTjaNJj1Q-FdYT2OjNkWL28h-jm-7fr8x948_vi5_nZBts1ExOmwMDwZQPZNWsjusZIEJJyxdqusdwSUzvuGlITsA5I065bLqGVHTAlDWGH6HTH3c7tCM5CmJIZ9Db5ZRYdjdfvM8Hf6j4-aCEZFWpdAMcvgBTLifKk7-KcyomyrplUQpJy7KKiO5VNMecE3WsHSvTim975posbevFNq1Lz5e1orxV_XSqCeifIJRV6SP9a_5_6DNMfpr8</recordid><startdate>20191105</startdate><enddate>20191105</enddate><creator>Kanaya, Noriko</creator><creator>Chang, Gregory</creator><creator>Wu, Xiwei</creator><creator>Saeki, Kohei</creator><creator>Bernal, Lauren</creator><creator>Shim, Hyun-Jeong</creator><creator>Wang, Jinhui</creator><creator>Warden, Charles</creator><creator>Yamamoto, Takuro</creator><creator>Li, Jay</creator><creator>Park, June-Soo</creator><creator>Synold, Timothy</creator><creator>Vonderfecht, Steve</creator><creator>Rakoff, Michele</creator><creator>Neuhausen, Susan L.</creator><creator>Chen, Shiuan</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1827-4486</orcidid><orcidid>https://orcid.org/0000-0002-4482-6926</orcidid></search><sort><creationdate>20191105</creationdate><title>Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland</title><author>Kanaya, Noriko ; Chang, Gregory ; Wu, Xiwei ; Saeki, Kohei ; Bernal, Lauren ; Shim, Hyun-Jeong ; Wang, Jinhui ; Warden, Charles ; Yamamoto, Takuro ; Li, Jay ; Park, June-Soo ; Synold, Timothy ; Vonderfecht, Steve ; Rakoff, Michele ; Neuhausen, Susan L. ; Chen, Shiuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-1e3ea419998f75a6f7a8e681493bf7c4c0a2d4d7020ecde07b5b48eb8fe398a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/1</topic><topic>17β-Estradiol</topic><topic>38/91</topic><topic>631/114</topic><topic>631/67/1347</topic><topic>64/60</topic><topic>692/163</topic><topic>82/51</topic><topic>Animals</topic><topic>Biology</topic><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Endocrine disruptors</topic><topic>Endocrine Disruptors - toxicity</topic><topic>Epidermal growth factor receptors</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Estradiol - toxicity</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogen receptors</topic><topic>Ethers</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Flame retardants</topic><topic>Flame Retardants - toxicity</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Halogenated Diphenyl Ethers - toxicity</topic><topic>Household products</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunomodulation</topic><topic>Immunoregulation</topic><topic>Life Sciences</topic><topic>Macrophages</topic><topic>Mammary gland</topic><topic>Mammary Glands, Animal - drug effects</topic><topic>Mammary Glands, Animal - metabolism</topic><topic>Mammary Glands, Animal - pathology</topic><topic>Menopause</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Ovariectomy</topic><topic>Polybrominated diphenyl ethers</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA-Seq</topic><topic>Sequence analysis</topic><topic>Single-Cell Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kanaya, Noriko</creatorcontrib><creatorcontrib>Chang, Gregory</creatorcontrib><creatorcontrib>Wu, Xiwei</creatorcontrib><creatorcontrib>Saeki, Kohei</creatorcontrib><creatorcontrib>Bernal, Lauren</creatorcontrib><creatorcontrib>Shim, Hyun-Jeong</creatorcontrib><creatorcontrib>Wang, Jinhui</creatorcontrib><creatorcontrib>Warden, Charles</creatorcontrib><creatorcontrib>Yamamoto, Takuro</creatorcontrib><creatorcontrib>Li, Jay</creatorcontrib><creatorcontrib>Park, June-Soo</creatorcontrib><creatorcontrib>Synold, Timothy</creatorcontrib><creatorcontrib>Vonderfecht, Steve</creatorcontrib><creatorcontrib>Rakoff, Michele</creatorcontrib><creatorcontrib>Neuhausen, Susan L.</creatorcontrib><creatorcontrib>Chen, Shiuan</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Communications biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kanaya, Noriko</au><au>Chang, Gregory</au><au>Wu, Xiwei</au><au>Saeki, Kohei</au><au>Bernal, Lauren</au><au>Shim, Hyun-Jeong</au><au>Wang, Jinhui</au><au>Warden, Charles</au><au>Yamamoto, Takuro</au><au>Li, Jay</au><au>Park, June-Soo</au><au>Synold, Timothy</au><au>Vonderfecht, Steve</au><au>Rakoff, Michele</au><au>Neuhausen, Susan L.</au><au>Chen, Shiuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland</atitle><jtitle>Communications biology</jtitle><stitle>Commun Biol</stitle><addtitle>Commun Biol</addtitle><date>2019-11-05</date><risdate>2019</risdate><volume>2</volume><issue>1</issue><spage>406</spage><pages>406-</pages><artnum>406</artnum><issn>2399-3642</issn><eissn>2399-3642</eissn><abstract>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 17β-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.
Kanaya et al. show that endocrine-disrupting chemicals polybrominated diphenyl ethers (PBDEs) enhance 17β-estradiol-mediated regrowth of mammary glands. This study suggests that PBDE may increase the risk of developing breast cancer by regulating the growth of estrogen-responsive luminal epithelial cells and the immune response.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31701034</pmid><doi>10.1038/s42003-019-0618-9</doi><orcidid>https://orcid.org/0000-0002-1827-4486</orcidid><orcidid>https://orcid.org/0000-0002-4482-6926</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2399-3642 |
| ispartof | Communications biology, 2019-11, Vol.2 (1), p.406, Article 406 |
| issn | 2399-3642 2399-3642 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6831695 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA/Free Journals; PubMed Central Open Access |
| subjects | 13/1 17β-Estradiol 38/91 631/114 631/67/1347 64/60 692/163 82/51 Animals Biology Biomedical and Life Sciences Breast cancer Endocrine disruptors Endocrine Disruptors - toxicity Epidermal growth factor receptors Epithelial cells Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology Estradiol - toxicity Estrogen Receptor alpha - metabolism Estrogen receptors Ethers Female Fibroblasts Fibroblasts - drug effects Fibroblasts - metabolism Fibroblasts - pathology Flame retardants Flame Retardants - toxicity Gene expression Gene Expression Profiling Halogenated Diphenyl Ethers - toxicity Household products Humans Immune response Immunomodulation Immunoregulation Life Sciences Macrophages Mammary gland Mammary Glands, Animal - drug effects Mammary Glands, Animal - metabolism Mammary Glands, Animal - pathology Menopause Mice Mice, Inbred BALB C Monocyte chemoattractant protein 1 Ovariectomy Polybrominated diphenyl ethers Receptors, Progesterone - metabolism Ribonucleic acid RNA RNA-Seq Sequence analysis Single-Cell Analysis |
| title | Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T07%3A01%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Single-cell%20RNA-sequencing%20analysis%20of%20estrogen-%20and%20endocrine-disrupting%20chemical-induced%20reorganization%20of%20mouse%20mammary%20gland&rft.jtitle=Communications%20biology&rft.au=Kanaya,%20Noriko&rft.date=2019-11-05&rft.volume=2&rft.issue=1&rft.spage=406&rft.pages=406-&rft.artnum=406&rft.issn=2399-3642&rft.eissn=2399-3642&rft_id=info:doi/10.1038/s42003-019-0618-9&rft_dat=%3Cproquest_pubme%3E2389680364%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2389680364&rft_id=info:pmid/31701034&rfr_iscdi=true |