{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:42:39Z","timestamp":1787226159918,"version":"build-2736575974"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA222560"],"award-info":[{"award-number":["R01 CA222560"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-15-1-0100"],"award-info":[{"award-number":["W81XWH-15-1-0100"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008035","name":"Harvard Stem Cell Institute","doi-asserted-by":"publisher","award":["SG-0062-10"],"award-info":[{"award-number":["SG-0062-10"]}],"id":[{"id":"10.13039\/100008035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mammary Gland Biol Neoplasia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Lineage tracing is a fundamental tool in developmental biology and cancer research, providing critical insights into cell fate decisions, tissue homeostasis and tumor initiation. The mammary gland is a highly dynamic organ with a complex cellular hierarchy, making it an ideal system for lineage-tracing studies. Classic approaches, such as tamoxifen-inducible CreER\/loxP recombination, have significantly advanced our understanding of mammary epithelial cell (MEC) differentiation, homeostasis, and transformation. However, these methods have limitations, including potential effects of tamoxifen on estrogen signaling, low mammary gland specificity, and the requirement for transgenic model creation and mouse breeding. Adenovirus-Cre (Ad-Cre)-based lineage tracing has emerged as a powerful alternative, enabling rapid and organ-specific recombination. This review provides a comprehensive evaluation of the Ad-Cre approach in mammary gland biology, comparing its efficiency, specificity, and technical advantages over the CreER-based method. We discuss applications of Ad-Cre intraductal injection-based lineage tracing in mapping MEC fates, identifying the cellular origins of breast cancer, and modeling tumor progression. Additionally, we highlight its ability to induce genetic marking at a clonal level, facilitating precise investigations into MEC plasticity and tumor cell heterogeneity. Despite its advantages, Ad-Cre lineage tracing also presents challenges, such as low cell-targeting efficiency and potential effect on the mammary gland immune microenvironment. Future advancements, including the integration of CRISPR-based barcoding, may further enhance its utility for high-resolution fate mapping. By summarizing recent advancements and comparative analyses, this review underscores the significance of Ad-Cre lineage tracing as a versatile and powerful tool in mammary gland biology and breast cancer research.<\/jats:p>","DOI":"10.1007\/s10911-025-09584-6","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T04:55:07Z","timestamp":1751864107000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intraductal Injection of Adenoviruses to Perform Lineage Tracing in the Mammary Gland"],"prefix":"10.1007","volume":"30","author":[{"given":"Xueqing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-0885","authenticated-orcid":false,"given":"Zhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"issue":"8","key":"9584_CR1","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1242\/dev.121.8.2595","volume":"121","author":"K Woo","year":"1995","unstructured":"Woo K, Fraser SE. Order and coherence in the fate map of the zebrafish nervous system. Development. 1995;121(8):2595\u2013609.","journal-title":"Development"},{"key":"9584_CR2","first-page":"325","volume":"106","author":"CA Giurumescu","year":"2011","unstructured":"Giurumescu CA, Chisholm AD. Cell identification and cell lineage analysis. Methods Cell Biol. 2011;106:325\u201341.","journal-title":"Methods Cell Biol"},{"issue":"11","key":"9584_CR3","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1002\/stem.2123","volume":"33","author":"YC Hsu","year":"2015","unstructured":"Hsu YC. Theory and practice of lineage tracing. Stem Cells. 2015;33(11):3197\u2013204.","journal-title":"Stem Cells"},{"key":"9584_CR4","doi-asserted-by":"publisher","unstructured":"Mateos-White I, et al. Double in utero electroporation to target temporally and spatially separated cell populations. J Vis Exp. 2020(160). https:\/\/doi.org\/10.3791\/61046.","DOI":"10.3791\/61046"},{"issue":"6","key":"9584_CR5","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1002\/dvdy.21174","volume":"236","author":"DA Stark","year":"2007","unstructured":"Stark DA, Kulesa PM. An in vivo comparison of photoactivatable fluorescent proteins in an avian embryo model. Dev Dyn. 2007;236(6):1583\u201394.","journal-title":"Dev Dyn"},{"issue":"1","key":"9584_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00534-010-0307-z","volume":"18","author":"Y Kawaguchi","year":"2011","unstructured":"Kawaguchi Y, Takaori K, Uemoto S. Genetic lineage tracing, a powerful tool to investigate the embryonic organogenesis and adult organ maintenance of the pancreas. J Hepatobiliary Pancreat Sci. 2011;18(1):1\u20135.","journal-title":"J Hepatobiliary Pancreat Sci"},{"key":"9584_CR7","doi-asserted-by":"crossref","unstructured":"Carlone DL. Identifying adult stem cells using Cre-Mediated lineage tracing. Curr Protoc Stem Cell Biol. 2016;36:5A.2.1-5A.2.18.","DOI":"10.1002\/9780470151808.sc05a02s36"},{"key":"9584_CR8","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/978-1-4939-2519-3_11","volume":"1293","author":"R van Amerongen","year":"2015","unstructured":"van Amerongen R. Lineage tracing in the mammary gland using cre\/lox technology and fluorescent reporter alleles. Methods Mol Biol. 2015;1293:187\u2013211.","journal-title":"Methods Mol Biol"},{"key":"9584_CR9","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.neubiorev.2019.12.013","volume":"108","author":"S Navabpour","year":"2020","unstructured":"Navabpour S, Kwapis JL, Jarome TJ. A neuroscientist\u2019s guide to Transgenic mice and other genetic tools. Neurosci Biobehav Rev. 2020;108:732\u201348.","journal-title":"Neurosci Biobehav Rev"},{"key":"9584_CR10","doi-asserted-by":"publisher","first-page":"115045","DOI":"10.1016\/j.biopha.2023.115045","volume":"165","author":"MY Chen","year":"2023","unstructured":"Chen MY, et al. A review of Tamoxifen administration regimen optimization for cre\/loxp system in mouse bone study. Biomed Pharmacother. 2023;165:115045.","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"9584_CR11","doi-asserted-by":"publisher","first-page":"147","DOI":"10.5625\/lar.2018.34.4.147","volume":"34","author":"H Kim","year":"2018","unstructured":"Kim H, et al. Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes. Lab Anim Res. 2018;34(4):147\u201359.","journal-title":"Lab Anim Res"},{"issue":"6","key":"9584_CR12","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.stemcr.2014.04.004","volume":"2","author":"L Tao","year":"2014","unstructured":"Tao L, et al. Lineage tracing of mammary epithelial cells using Cell-Type-Specific Cre-Expressing adenoviruses. Stem Cell Rep. 2014;2(6):770\u20139.","journal-title":"Stem Cell Rep"},{"key":"9584_CR13","doi-asserted-by":"crossref","unstructured":"Wust RCI, Houtkooper RH, Auwerx J. Confounding factors from inducible systems for Spatiotemporal gene expression regulation. J Cell Biol. 2020;219(7):e202003031.","DOI":"10.1083\/jcb.202003031"},{"issue":"11","key":"9584_CR14","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1101\/gad.280057.116","volume":"30","author":"A Wuidart","year":"2016","unstructured":"Wuidart A, et al. Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells. Genes Dev. 2016;30(11):1261\u201377.","journal-title":"Genes Dev"},{"issue":"19","key":"9584_CR15","doi-asserted-by":"publisher","first-page":"6413","DOI":"10.1074\/jbc.REV120.011631","volume":"295","author":"K Liu","year":"2020","unstructured":"Liu K, Jin H, Zhou B. Genetic lineage tracing with multiple DNA recombinases: A user\u2019s guide for conducting more precise cell fate mapping studies. J Biol Chem. 2020;295(19):6413\u201324.","journal-title":"J Biol Chem"},{"issue":"7072","key":"9584_CR16","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/nature04372","volume":"439","author":"M Shackleton","year":"2006","unstructured":"Shackleton M, et al. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439(7072):84\u20138.","journal-title":"Nature"},{"issue":"7079","key":"9584_CR17","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/nature04496","volume":"439","author":"J Stingl","year":"2006","unstructured":"Stingl J, et al. Purification and unique properties of mammary epithelial stem cells. Nature. 2006;439(7079):993\u20137.","journal-title":"Nature"},{"issue":"2","key":"9584_CR18","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.stem.2011.12.018","volume":"10","author":"BT Spike","year":"2012","unstructured":"Spike BT, et al. A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. Cell Stem Cell. 2012;10(2):183\u201397.","journal-title":"Cell Stem Cell"},{"issue":"8","key":"9584_CR19","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1007\/s00018-014-1817-7","volume":"72","author":"S Sale","year":"2015","unstructured":"Sale S, Pavelic K. Mammary lineage tracing: the coming of age. Cell Mol Life Sci. 2015;72(8):1577\u201383.","journal-title":"Cell Mol Life Sci"},{"key":"9584_CR20","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41523-017-0018-6","volume":"3","author":"CL Trejo","year":"2017","unstructured":"Trejo CL, et al. Lgr5 is a marker for fetal mammary stem cells, but is not essential for stem cell activity or tumorigenesis. NPJ Breast Cancer. 2017;3:16.","journal-title":"NPJ Breast Cancer"},{"issue":"6","key":"9584_CR21","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/s41556-018-0095-2","volume":"20","author":"A Wuidart","year":"2018","unstructured":"Wuidart A, et al. Early lineage segregation of multipotent embryonic mammary gland progenitors. Nat Cell Biol. 2018;20(6):666\u201376.","journal-title":"Nat Cell Biol"},{"issue":"10","key":"9584_CR22","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/ncb3025","volume":"16","author":"MD Prater","year":"2014","unstructured":"Prater MD, et al. Mammary stem cells have myoepithelial cell properties. Nat Cell Biol. 2014;16(10):942\u201350.","journal-title":"Nat Cell Biol"},{"issue":"2","key":"9584_CR23","doi-asserted-by":"publisher","first-page":"e1002069","DOI":"10.1371\/journal.pbio.1002069","volume":"13","author":"V Rodilla","year":"2015","unstructured":"Rodilla V, et al. Luminal progenitors restrict their lineage potential during mammary gland development. PLoS Biol. 2015;13(2):e1002069.","journal-title":"PLoS Biol"},{"issue":"7372","key":"9584_CR24","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/nature10573","volume":"479","author":"A Van Keymeulen","year":"2011","unstructured":"Van Keymeulen A, et al. Distinct stem cells contribute to mammary gland development and maintenance. Nature. 2011;479(7372):189\u201393.","journal-title":"Nature"},{"issue":"6","key":"9584_CR25","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/s41556-018-0108-1","volume":"20","author":"AM Lilja","year":"2018","unstructured":"Lilja AM, et al. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland. Nat Cell Biol. 2018;20(6):677\u201387.","journal-title":"Nat Cell Biol"},{"issue":"7488","key":"9584_CR26","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/nature12948","volume":"506","author":"AC Rios","year":"2014","unstructured":"Rios AC, et al. In situ identification of bipotent stem cells in the mammary gland. Nature. 2014;506(7488):322\u20137.","journal-title":"Nature"},{"issue":"1","key":"9584_CR27","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.stemcr.2015.05.014","volume":"5","author":"L Tao","year":"2015","unstructured":"Tao L, van Bragt MP, Li Z. A Long-Lived luminal subpopulation enriched with alveolar progenitors serves as cellular origin of heterogeneous mammary tumors. Stem Cell Rep. 2015;5(1):60\u201374.","journal-title":"Stem Cell Rep"},{"issue":"7","key":"9584_CR28","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1016\/j.celrep.2017.07.066","volume":"20","author":"A Van Keymeulen","year":"2017","unstructured":"Van Keymeulen A, et al. Lineage-Restricted mammary stem cells sustain the development, homeostasis, and regeneration of the Estrogen receptor positive lineage. Cell Rep. 2017;20(7):1525\u201332.","journal-title":"Cell Rep"},{"issue":"12","key":"9584_CR29","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1016\/j.celrep.2017.02.071","volume":"18","author":"C Wang","year":"2017","unstructured":"Wang C, et al. Lineage-Biased stem cells maintain Estrogen-Receptor-Positive and -Negative mouse mammary luminal lineages. Cell Rep. 2017;18(12):2825\u201335.","journal-title":"Cell Rep"},{"issue":"12","key":"9584_CR30","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/sj.gt.3301197","volume":"7","author":"RD Anderson","year":"2000","unstructured":"Anderson RD, et al. A simple method for the rapid generation of Recombinant adenovirus vectors. Gene Ther. 2000;7(12):1034\u20138.","journal-title":"Gene Ther"},{"issue":"3","key":"9584_CR31","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S0022-5223(03)00082-5","volume":"126","author":"D Chu","year":"2003","unstructured":"Chu D, et al. Direct comparison of efficiency and stability of gene transfer into the mammalian heart using adeno-associated virus versus adenovirus vectors. J Thorac Cardiovasc Surg. 2003;126(3):671\u20139.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"9584_CR32","doi-asserted-by":"publisher","unstructured":"Xiang D, Tao L, Li Z. Modeling breast Cancer via an intraductal injection of Cre-expressing adenovirus into the mouse mammary gland. J Vis Exp. 2019;148https:\/\/doi.org\/10.3791\/59502.","DOI":"10.3791\/59502"},{"key":"9584_CR33","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-213X-1-4","volume":"1","author":"S Srinivas","year":"2001","unstructured":"Srinivas S, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol. 2001;1:4.","journal-title":"BMC Dev Biol"},{"issue":"6","key":"9584_CR34","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.ccr.2011.04.019","volume":"19","author":"KD Sutherland","year":"2011","unstructured":"Sutherland KD, et al. Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell. 2011;19(6):754\u201364.","journal-title":"Cancer Cell"},{"issue":"8","key":"9584_CR35","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/nm.2000","volume":"15","author":"E Lim","year":"2009","unstructured":"Lim E, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009;15(8):907\u201313.","journal-title":"Nat Med"},{"issue":"3","key":"9584_CR36","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.stem.2010.07.010","volume":"7","author":"G Molyneux","year":"2010","unstructured":"Molyneux G, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell. 2010;7(3):403\u201317.","journal-title":"Cell Stem Cell"},{"issue":"2","key":"9584_CR37","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.stem.2010.12.007","volume":"8","author":"TA Proia","year":"2011","unstructured":"Proia TA, et al. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell. 2011;8(2):149\u201363.","journal-title":"Cell Stem Cell"},{"issue":"7","key":"9584_CR38","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1242\/dev.121.7.2079","volume":"121","author":"GW Robinson","year":"1995","unstructured":"Robinson GW, et al. Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation. Development. 1995;121(7):2079\u201390.","journal-title":"Development"},{"key":"9584_CR39","doi-asserted-by":"publisher","first-page":"14431","DOI":"10.1038\/ncomms14431","volume":"8","author":"L Tao","year":"2017","unstructured":"Tao L, et al. Induced p53 loss in mouse luminal cells causes clonal expansion and development of mammary tumours. Nat Commun. 2017;8:14431.","journal-title":"Nat Commun"},{"issue":"3","key":"9584_CR40","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/path.4096","volume":"228","author":"KE de Visser","year":"2012","unstructured":"de Visser KE, et al. Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland. J Pathol. 2012;228(3):300\u20139.","journal-title":"J Pathol"},{"issue":"5","key":"9584_CR41","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/ncb2725","volume":"15","author":"S Sale","year":"2013","unstructured":"Sale S, Lafkas D, Artavanis-Tsakonas S. Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages. Nat Cell Biol. 2013;15(5):451\u201360.","journal-title":"Nat Cell Biol"},{"issue":"23","key":"9584_CR42","doi-asserted-by":"publisher","first-page":"5605","DOI":"10.3390\/cancers15235605","volume":"15","author":"MN Wicker","year":"2023","unstructured":"Wicker MN, Wagner KU. Cellular plasticity in mammary gland development and breast Cancer. Cancers (Basel). 2023;15(23):5605.","journal-title":"Cancers (Basel)."},{"key":"9584_CR43","doi-asserted-by":"crossref","unstructured":"Lloyd-Lewis B, et al. Neutral lineage tracing of proliferative embryonic and adult mammary stem\/progenitor cells. Development. 2018;145(14):dev164079.","DOI":"10.1242\/dev.164079"},{"issue":"7641","key":"9584_CR44","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nature21046","volume":"542","author":"CL Scheele","year":"2017","unstructured":"Scheele CL, et al. Identity and dynamics of mammary stem cells during branching morphogenesis. Nature. 2017;542(7641):313\u20137.","journal-title":"Nature"},{"issue":"5","key":"9584_CR45","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/S1535-6108(02)00180-0","volume":"2","author":"C Tognon","year":"2002","unstructured":"Tognon C, et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002;2(5):367\u201376.","journal-title":"Cancer Cell"},{"issue":"7567","key":"9584_CR46","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nature14669","volume":"525","author":"S Koren","year":"2015","unstructured":"Koren S, et al. PIK3CA induces multipotency and multi-lineage mammary tumours. Nature. 2015;525(7567):114\u20138.","journal-title":"Nature"},{"issue":"7567","key":"9584_CR47","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/nature14665","volume":"525","author":"A Van Keymeulen","year":"2015","unstructured":"Van Keymeulen A, et al. Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity. Nature. 2015;525(7567):119\u201323.","journal-title":"Nature"},{"issue":"12","key":"9584_CR48","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1158\/2159-8290.CD-21-0865","volume":"12","author":"E Langille","year":"2022","unstructured":"Langille E, et al. Loss of epigenetic regulation disrupts lineage integrity, induces aberrant alveogenesis, and promotes breast Cancer. Cancer Discov. 2022;12(12):2930\u201353.","journal-title":"Cancer Discov"},{"issue":"1","key":"9584_CR49","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.cell.2019.06.002","volume":"178","author":"H Wang","year":"2019","unstructured":"Wang H, et al. Inadequate DNA damage repair promotes mammary transdifferentiation, leading to BRCA1 breast Cancer. Cell. 2019;178(1):135\u2013e15119.","journal-title":"Cell"},{"issue":"1","key":"9584_CR50","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13058-022-01566-4","volume":"24","author":"L Szabova","year":"2022","unstructured":"Szabova L, et al. Loss of Brca1 and Trp53 in adult mouse mammary ductal epithelium results in development of hormone receptor-positive or hormone receptor-negative tumors, depending on inactivation of Rb family proteins. Breast Cancer Res. 2022;24(1):75.","journal-title":"Breast Cancer Res"},{"issue":"1","key":"9584_CR51","doi-asserted-by":"publisher","first-page":"7198","DOI":"10.1038\/s41467-022-34864-8","volume":"13","author":"JG Kern","year":"2022","unstructured":"Kern JG, et al. Inactivation of LATS1\/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas. Nat Commun. 2022;13(1):7198.","journal-title":"Nat Commun"},{"issue":"22","key":"9584_CR52","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1101\/gad.268185.115","volume":"29","author":"N Furth","year":"2015","unstructured":"Furth N, et al. Down-regulation of LATS kinases alters p53 to promote cell migration. Genes Dev. 2015;29(22):2325\u201330.","journal-title":"Genes Dev"},{"issue":"11","key":"9584_CR53","doi-asserted-by":"publisher","first-page":"R125","DOI":"10.1186\/gb-2013-14-11-r125","volume":"14","author":"AD Pfefferle","year":"2013","unstructured":"Pfefferle AD, et al. Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts. Genome Biol. 2013;14(11):R125.","journal-title":"Genome Biol"},{"issue":"44","key":"9584_CR54","doi-asserted-by":"publisher","first-page":"7017","DOI":"10.1038\/s41388-019-0923-2","volume":"38","author":"X Hu","year":"2019","unstructured":"Hu X, et al. LSD1 suppresses invasion, migration and metastasis of luminal breast cancer cells via activation of GATA3 and repression of TRIM37 expression. Oncogene. 2019;38(44):7017\u201334.","journal-title":"Oncogene"},{"issue":"3","key":"9584_CR55","doi-asserted-by":"publisher","first-page":"e33529","DOI":"10.1371\/journal.pone.0033529","volume":"7","author":"RB Reinert","year":"2012","unstructured":"Reinert RB, et al. Tamoxifen-Induced Cre-loxP recombination is prolonged in pancreatic islets of adult mice. PLoS ONE. 2012;7(3):e33529.","journal-title":"PLoS ONE"},{"issue":"4","key":"9584_CR56","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1186\/s13058-014-0411-0","volume":"16","author":"M Shehata","year":"2014","unstructured":"Shehata M, et al. The influence of Tamoxifen on normal mouse mammary gland homeostasis. Breast Cancer Res. 2014;16(4):411.","journal-title":"Breast Cancer Res"},{"issue":"3","key":"9584_CR57","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.stem.2013.01.003","volume":"12","author":"Y Zhu","year":"2013","unstructured":"Zhu Y, et al. Apoptosis differently affects lineage tracing of Lgr5 and Bmi1 intestinal stem cell populations. Cell Stem Cell. 2013;12(3):298\u2013303.","journal-title":"Cell Stem Cell"},{"issue":"16","key":"9584_CR58","doi-asserted-by":"publisher","first-page":"9209","DOI":"10.1073\/pnas.161269798","volume":"98","author":"A Loonstra","year":"2001","unstructured":"Loonstra A, et al. Growth Inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc Natl Acad Sci U S A. 2001;98(16):9209\u201314.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9584_CR59","doi-asserted-by":"publisher","first-page":"975803","DOI":"10.3389\/fimmu.2022.975803","volume":"13","author":"HCJ Ertl","year":"2022","unstructured":"Ertl HCJ. Immunogenicity and toxicity of AAV gene therapy. Front Immunol. 2022;13:975803.","journal-title":"Front Immunol"},{"issue":"1","key":"9584_CR60","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev-virology-092818-015550","volume":"6","author":"UF Greber","year":"2019","unstructured":"Greber UF, Flatt JW. Adenovirus entry: from infection to immunity. Annu Rev Virol. 2019;6(1):177\u201397.","journal-title":"Annu Rev Virol"},{"issue":"9","key":"9584_CR61","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.3390\/v15091801","volume":"15","author":"Y Wang","year":"2023","unstructured":"Wang Y, Shao W. Innate immune response to viral vectors in gene therapy. Viruses. 2023;15(9):1801.","journal-title":"Viruses."},{"issue":"10","key":"9584_CR62","doi-asserted-by":"publisher","first-page":"5801","DOI":"10.1128\/JVI.77.10.5801-5809.2003","volume":"77","author":"TD Russell","year":"2003","unstructured":"Russell TD, et al. Transduction of the mammary epithelium with adenovirus vectors in vivo. J Virol. 2003;77(10):5801\u20139.","journal-title":"J Virol"},{"issue":"3\u20134","key":"9584_CR63","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s10911-022-09526-6","volume":"27","author":"AJ Twigger","year":"2022","unstructured":"Twigger AJ, et al. Thirteenth annual ENBDC workshop: methods in mammary gland biology and breast Cancer. J Mammary Gland Biol Neoplasia. 2022;27(3\u20134):233\u20139.","journal-title":"J Mammary Gland Biol Neoplasia"},{"issue":"6","key":"9584_CR64","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1016\/j.cell.2020.04.048","volume":"181","author":"S Bowling","year":"2020","unstructured":"Bowling S, et al. An engineered CRISPR-Cas9 mouse line for simultaneous readout of lineage histories and gene expression profiles in single cells. Cell. 2020;181(6):1410\u2013e142227.","journal-title":"Cell"},{"key":"9584_CR65","doi-asserted-by":"crossref","unstructured":"Kalhor R, et al. Developmental barcoding of whole mouse via homing CRISPR. Science. 2018;361(6405):eaat9804.","DOI":"10.1126\/science.aat9804"},{"issue":"4","key":"9584_CR66","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1038\/s41596-020-00485-y","volume":"16","author":"K Leeper","year":"2021","unstructured":"Leeper K, et al. Lineage barcoding in mice with homing CRISPR. Nat Protoc. 2021;16(4):2088\u2013108.","journal-title":"Nat Protoc"},{"issue":"2","key":"9584_CR67","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.cell.2014.09.014","volume":"159","author":"RJ Platt","year":"2014","unstructured":"Platt RJ, et al. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell. 2014;159(2):440\u201355.","journal-title":"Cell"}],"container-title":["Journal of Mammary Gland Biology and Neoplasia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10911-025-09584-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10911-025-09584-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10911-025-09584-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T06:02:50Z","timestamp":1751868170000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10911-025-09584-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["9584"],"URL":"https:\/\/doi.org\/10.1007\/s10911-025-09584-6","relation":{},"ISSN":["1083-3021","1573-7039"],"issn-type":[{"value":"1083-3021","type":"print"},{"value":"1573-7039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]},"assertion":[{"value":"31 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10"}}