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But, how exactly tumors arise from a few malignant cells within an intact epithelium is a central, yet unanswered question. This is mainly due to the inaccessibility of this process to longitudinal imaging together with a lack of systems that model the progression of a fraction of transformed cells within a tissue. Here, we developed a new methodology based on primary mouse mammary epithelial acini, where oncogenes can be switched on in single cells within an otherwise normal epithelial cell layer. We combine this stochastic breast tumor induction model with inverted light-sheet imaging to study single-cell behavior for up to four days and analyze cell fates utilizing a newly developed image-data analysis workflow. The power of this integrated approach is illustrated by us finding that small local clusters of transformed cells form tumors while isolated transformed cells do not.<\/jats:p>","DOI":"10.7554\/elife.54066","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T20:00:39Z","timestamp":1595275239000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.54066","source":"Crossref","is-referenced-by-count":40,"title":["Tracking cells in epithelial acini by light sheet microscopy reveals proximity effects in breast cancer initiation"],"prefix":"10.7554","volume":"9","author":[{"given":"Ashna","family":"Alladin","sequence":"first","affiliation":[{"name":"Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Chaible","sequence":"additional","affiliation":[{"name":"Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Garcia del Valle","sequence":"additional","affiliation":[{"name":"Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reither","family":"Sabine","sequence":"additional","affiliation":[{"name":"Advanced Light Microscopy Facility, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Loeschinger","sequence":"additional","affiliation":[{"name":"Luxendo Light-Sheet, Bruker Corporation, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Wachsmuth","sequence":"additional","affiliation":[{"name":"Luxendo Light-Sheet, Bruker Corporation, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6867-9425","authenticated-orcid":true,"given":"Jean-Karim","family":"H\u00e9rich\u00e9","sequence":"additional","affiliation":[{"name":"Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Tischer","sequence":"additional","affiliation":[{"name":"Centre for Bioimage Analysis, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-4466","authenticated-orcid":true,"given":"Martin","family":"Jechlinger","sequence":"additional","affiliation":[{"name":"Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1111\/dgd.12062","article-title":"Reporter mouse lines for fluorescence imaging","volume":"55","author":"Abe","year":"2013","journal-title":"Development, Growth & Differentiation"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"8534","DOI":"10.1158\/0008-5472.CAN-04-1945","article-title":"Prognostic relevance of gene amplifications and coamplifications in breast Cancer","volume":"64","author":"Al-Kuraya","year":"2004","journal-title":"Cancer Research"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/nrclinonc.2011.177","article-title":"Treatment of HER2-positive breast Cancer: current status and future perspectives","volume":"9","author":"Arteaga","year":"2012","journal-title":"Nature Reviews Clinical Oncology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nature Medicine"},{"key":"bib5","article-title":"3\/4D Image Visualization and Analysis Software","volume-title":"Imaris","author":"Bitplane AG","year":"2020","unstructured":"Bitplane AG. 2020. 3\/4D Image Visualization and Analysis Software. 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