Kyungchan Kim , Jamie Wann , Hyeong-Geug Kim , Jisun So , Evan D. Rosen , Hyun Cheol Roh
{"title":"解偶联蛋白 1 驱动的 Cre(Ucp1-Cre)在乳腺和各种非脂肪组织的上皮细胞中表达","authors":"Kyungchan Kim , Jamie Wann , Hyeong-Geug Kim , Jisun So , Evan D. Rosen , Hyun Cheol Roh","doi":"10.1016/j.molmet.2024.101948","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Uncoupling protein 1 (UCP1), a mitochondrial protein responsible for nonshivering thermogenesis in adipose tissue, serves as a distinct marker for thermogenic brown and beige adipocytes. <em>Ucp1-Cre</em> mice are thus widely used to genetically manipulate these thermogenic adipocytes. However, evidence suggests that UCP1 may also be expressed in non-adipocyte cell types. In this study, we investigated the presence of UCP1 expression in different mouse tissues that have not been previously reported.</p></div><div><h3>Methods</h3><p>We employed <em>Ucp1-Cre</em> mice crossed with Cre-inducible transgenic reporter Nuclear tagging and Translating Ribosome Affinity Purification (NuTRAP) mice to investigate <em>Ucp1</em>-<em>Cre</em> expression in various tissues of adult female mice and developing embryos. Tamoxifen-inducible <em>Ucp1-CreERT2</em> mice crossed with NuTRAP mice were used to assess active <em>Ucp1</em> expression in adult mice. Immunostaining, RNA analysis, and single-cell/nucleus RNA-seq (sc/snRNA-seq) data analysis were performed to determine the expression of endogenous UCP1 and <em>Ucp1-Cre</em>-driven reporter expression. We also investigated the impact of UCP1 deficiency on mammary gland development and function using <em>Ucp1</em>-knockout (KO) mice.</p></div><div><h3>Results</h3><p><em>Ucp1-Cre</em> expression was observed in the mammary glands within the inguinal white adipose tissue of female <em>Ucp1-Cre</em>; NuTRAP mice. <em>Ucp1-Cre</em> was activated during embryonic development in various tissues, including mammary glands, as well as in the brain, kidneys, eyes, and ears, specifically in epithelial cells in these organs. However, <em>Ucp1-CreERT2</em> showed no or only partial activation in these tissues of adult mice, indicating the potential for low or transient expression of endogenous <em>Ucp1</em>. While sc/snRNA-seq data suggest potential expression of UCP1 in mammary epithelial cells in adult mice and humans, <em>Ucp1</em>-KO female mice displayed normal mammary gland development and function.</p></div><div><h3>Conclusions</h3><p>Our findings reveal widespread <em>Ucp1-Cre</em> expression in various non-adipose tissue types, starting during early development. These results highlight the importance of exercising caution when interpreting data and devising experiments involving <em>Ucp1-Cre</em> mice.</p></div>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":null,"pages":null},"PeriodicalIF":7.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212877824000796/pdfft?md5=2dd886159b3e290fb7fce24fd7d83585&pid=1-s2.0-S2212877824000796-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Uncoupling protein 1-driven Cre (Ucp1-Cre) is expressed in the epithelial cells of mammary glands and various non-adipose tissues\",\"authors\":\"Kyungchan Kim , Jamie Wann , Hyeong-Geug Kim , Jisun So , Evan D. Rosen , Hyun Cheol Roh\",\"doi\":\"10.1016/j.molmet.2024.101948\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Uncoupling protein 1 (UCP1), a mitochondrial protein responsible for nonshivering thermogenesis in adipose tissue, serves as a distinct marker for thermogenic brown and beige adipocytes. <em>Ucp1-Cre</em> mice are thus widely used to genetically manipulate these thermogenic adipocytes. However, evidence suggests that UCP1 may also be expressed in non-adipocyte cell types. In this study, we investigated the presence of UCP1 expression in different mouse tissues that have not been previously reported.</p></div><div><h3>Methods</h3><p>We employed <em>Ucp1-Cre</em> mice crossed with Cre-inducible transgenic reporter Nuclear tagging and Translating Ribosome Affinity Purification (NuTRAP) mice to investigate <em>Ucp1</em>-<em>Cre</em> expression in various tissues of adult female mice and developing embryos. Tamoxifen-inducible <em>Ucp1-CreERT2</em> mice crossed with NuTRAP mice were used to assess active <em>Ucp1</em> expression in adult mice. Immunostaining, RNA analysis, and single-cell/nucleus RNA-seq (sc/snRNA-seq) data analysis were performed to determine the expression of endogenous UCP1 and <em>Ucp1-Cre</em>-driven reporter expression. We also investigated the impact of UCP1 deficiency on mammary gland development and function using <em>Ucp1</em>-knockout (KO) mice.</p></div><div><h3>Results</h3><p><em>Ucp1-Cre</em> expression was observed in the mammary glands within the inguinal white adipose tissue of female <em>Ucp1-Cre</em>; NuTRAP mice. <em>Ucp1-Cre</em> was activated during embryonic development in various tissues, including mammary glands, as well as in the brain, kidneys, eyes, and ears, specifically in epithelial cells in these organs. However, <em>Ucp1-CreERT2</em> showed no or only partial activation in these tissues of adult mice, indicating the potential for low or transient expression of endogenous <em>Ucp1</em>. While sc/snRNA-seq data suggest potential expression of UCP1 in mammary epithelial cells in adult mice and humans, <em>Ucp1</em>-KO female mice displayed normal mammary gland development and function.</p></div><div><h3>Conclusions</h3><p>Our findings reveal widespread <em>Ucp1-Cre</em> expression in various non-adipose tissue types, starting during early development. These results highlight the importance of exercising caution when interpreting data and devising experiments involving <em>Ucp1-Cre</em> mice.</p></div>\",\"PeriodicalId\":18765,\"journal\":{\"name\":\"Molecular Metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2024-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2212877824000796/pdfft?md5=2dd886159b3e290fb7fce24fd7d83585&pid=1-s2.0-S2212877824000796-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212877824000796\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Metabolism","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212877824000796","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Uncoupling protein 1-driven Cre (Ucp1-Cre) is expressed in the epithelial cells of mammary glands and various non-adipose tissues
Objective
Uncoupling protein 1 (UCP1), a mitochondrial protein responsible for nonshivering thermogenesis in adipose tissue, serves as a distinct marker for thermogenic brown and beige adipocytes. Ucp1-Cre mice are thus widely used to genetically manipulate these thermogenic adipocytes. However, evidence suggests that UCP1 may also be expressed in non-adipocyte cell types. In this study, we investigated the presence of UCP1 expression in different mouse tissues that have not been previously reported.
Methods
We employed Ucp1-Cre mice crossed with Cre-inducible transgenic reporter Nuclear tagging and Translating Ribosome Affinity Purification (NuTRAP) mice to investigate Ucp1-Cre expression in various tissues of adult female mice and developing embryos. Tamoxifen-inducible Ucp1-CreERT2 mice crossed with NuTRAP mice were used to assess active Ucp1 expression in adult mice. Immunostaining, RNA analysis, and single-cell/nucleus RNA-seq (sc/snRNA-seq) data analysis were performed to determine the expression of endogenous UCP1 and Ucp1-Cre-driven reporter expression. We also investigated the impact of UCP1 deficiency on mammary gland development and function using Ucp1-knockout (KO) mice.
Results
Ucp1-Cre expression was observed in the mammary glands within the inguinal white adipose tissue of female Ucp1-Cre; NuTRAP mice. Ucp1-Cre was activated during embryonic development in various tissues, including mammary glands, as well as in the brain, kidneys, eyes, and ears, specifically in epithelial cells in these organs. However, Ucp1-CreERT2 showed no or only partial activation in these tissues of adult mice, indicating the potential for low or transient expression of endogenous Ucp1. While sc/snRNA-seq data suggest potential expression of UCP1 in mammary epithelial cells in adult mice and humans, Ucp1-KO female mice displayed normal mammary gland development and function.
Conclusions
Our findings reveal widespread Ucp1-Cre expression in various non-adipose tissue types, starting during early development. These results highlight the importance of exercising caution when interpreting data and devising experiments involving Ucp1-Cre mice.
期刊介绍:
Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction.
We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.