Reconstruction of dynamic mammary mini gland in vitro for normal physiology and oncogenesis
Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling. However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult s...
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| Veröffentlicht in: | Nature methods 2023-12, Vol.20 (12), p.2021-2033 |
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| creator | Yuan, Lei Xie, Shaofang Bai, Huiru Liu, Xiaoqin Cai, Pei Lu, Jing Wang, Chunhui Lin, Zuobao Li, Shuying Guo, Yajing Cai, Shang |
| description | Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling. However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult stem cell-derived mammary mini gland culture system that supports robust three-dimensional outgrowths recapitulating the morphology, scale, cellular context and transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signals and dynamic physiological cycles. We show that these mini glands were hormone responsive and could recapitulate the entire postnatal mammary development including puberty, estrus cycle, lactation and involution. We also observed that these mini glands maintained the presence of mammary stem cells and could also recapitulate the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, upon induction of oncogene expression in the mini glands, we observed tumor initiation in vitro and in vivo in a mouse model. Together, this study provides an experimental system that can support a dynamic miniature mammary gland for the study of physiologically relevant, complex biological processes.
A dynamic, hormone-responsive mammary gland organoid system that can mimic complex physiological processes in vitro. |
| doi_str_mv | 10.1038/s41592-023-02039-y |
| format | Article |
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A dynamic, hormone-responsive mammary gland organoid system that can mimic complex physiological processes in vitro.</description><identifier>ISSN: 1548-7091</identifier><identifier>EISSN: 1548-7105</identifier><identifier>DOI: 10.1038/s41592-023-02039-y</identifier><identifier>PMID: 37919421</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/136/142 ; 631/136/1660 ; 631/136/2060 ; 631/1647/767 ; 631/532/2064 ; Bioinformatics ; Biological activity ; Biological Microscopy ; Biological Techniques ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Cell culture ; Estrus cycle ; Extracellular matrix ; Heterogeneity ; In vivo methods and tests ; Lactation ; Life Sciences ; Mammary gland ; Mammary glands ; Organoids ; Physiology ; Proteomics ; Puberty ; Reconstruction ; Stem cells ; Tumorigenesis</subject><ispartof>Nature methods, 2023-12, Vol.20 (12), p.2021-2033</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Nature America, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-ed5d59aa051701fddc03c57e480b495e0e081366cd3b7a7b12ec2b417cf790d63</citedby><cites>FETCH-LOGICAL-c375t-ed5d59aa051701fddc03c57e480b495e0e081366cd3b7a7b12ec2b417cf790d63</cites><orcidid>0000-0003-0630-7719 ; 0009-0006-1378-7000</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41592-023-02039-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41592-023-02039-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37919421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Lei</creatorcontrib><creatorcontrib>Xie, Shaofang</creatorcontrib><creatorcontrib>Bai, Huiru</creatorcontrib><creatorcontrib>Liu, Xiaoqin</creatorcontrib><creatorcontrib>Cai, Pei</creatorcontrib><creatorcontrib>Lu, Jing</creatorcontrib><creatorcontrib>Wang, Chunhui</creatorcontrib><creatorcontrib>Lin, Zuobao</creatorcontrib><creatorcontrib>Li, Shuying</creatorcontrib><creatorcontrib>Guo, Yajing</creatorcontrib><creatorcontrib>Cai, Shang</creatorcontrib><title>Reconstruction of dynamic mammary mini gland in vitro for normal physiology and oncogenesis</title><title>Nature methods</title><addtitle>Nat Methods</addtitle><addtitle>Nat Methods</addtitle><description>Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling. However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult stem cell-derived mammary mini gland culture system that supports robust three-dimensional outgrowths recapitulating the morphology, scale, cellular context and transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signals and dynamic physiological cycles. We show that these mini glands were hormone responsive and could recapitulate the entire postnatal mammary development including puberty, estrus cycle, lactation and involution. We also observed that these mini glands maintained the presence of mammary stem cells and could also recapitulate the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, upon induction of oncogene expression in the mini glands, we observed tumor initiation in vitro and in vivo in a mouse model. Together, this study provides an experimental system that can support a dynamic miniature mammary gland for the study of physiologically relevant, complex biological processes.
A dynamic, hormone-responsive mammary gland organoid system that can mimic complex physiological processes in vitro.</description><subject>631/136/142</subject><subject>631/136/1660</subject><subject>631/136/2060</subject><subject>631/1647/767</subject><subject>631/532/2064</subject><subject>Bioinformatics</subject><subject>Biological activity</subject><subject>Biological Microscopy</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Cell culture</subject><subject>Estrus cycle</subject><subject>Extracellular matrix</subject><subject>Heterogeneity</subject><subject>In vivo methods and tests</subject><subject>Lactation</subject><subject>Life Sciences</subject><subject>Mammary gland</subject><subject>Mammary glands</subject><subject>Organoids</subject><subject>Physiology</subject><subject>Proteomics</subject><subject>Puberty</subject><subject>Reconstruction</subject><subject>Stem 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However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult stem cell-derived mammary mini gland culture system that supports robust three-dimensional outgrowths recapitulating the morphology, scale, cellular context and transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signals and dynamic physiological cycles. We show that these mini glands were hormone responsive and could recapitulate the entire postnatal mammary development including puberty, estrus cycle, lactation and involution. We also observed that these mini glands maintained the presence of mammary stem cells and could also recapitulate the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, upon induction of oncogene expression in the mini glands, we observed tumor initiation in vitro and in vivo in a mouse model. Together, this study provides an experimental system that can support a dynamic miniature mammary gland for the study of physiologically relevant, complex biological processes.
A dynamic, hormone-responsive mammary gland organoid system that can mimic complex physiological processes in vitro.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>37919421</pmid><doi>10.1038/s41592-023-02039-y</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-0630-7719</orcidid><orcidid>https://orcid.org/0009-0006-1378-7000</orcidid></addata></record> |
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| subjects | 631/136/142 631/136/1660 631/136/2060 631/1647/767 631/532/2064 Bioinformatics Biological activity Biological Microscopy Biological Techniques Biomedical and Life Sciences Biomedical Engineering/Biotechnology Cell culture Estrus cycle Extracellular matrix Heterogeneity In vivo methods and tests Lactation Life Sciences Mammary gland Mammary glands Organoids Physiology Proteomics Puberty Reconstruction Stem cells Tumorigenesis |
| title | Reconstruction of dynamic mammary mini gland in vitro for normal physiology and oncogenesis |
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