Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland.","authors":"Samantha Henry,&nbsp;Marygrace C Trousdell,&nbsp;Samantha L Cyrill,&nbsp;Yixin Zhao,&nbsp;Mary J Feigman,&nbsp;Julia M Bouhuis,&nbsp;Dominik A Aylard,&nbsp;Adam Siepel,&nbsp;Camila O Dos Santos","doi":"10.1007/s10911-021-09486-3","DOIUrl":"10.1007/s10911-021-09486-3","url":null,"abstract":"<p><p>The developing mammary gland depends on several transcription-dependent networks to define cellular identities and differentiation trajectories. Recent technological advancements that allow for single-cell profiling of gene expression have provided an initial picture into the epithelial cellular heterogeneity across the diverse stages of gland maturation. Still, a deeper dive into expanded molecular signatures would improve our understanding of the diversity of mammary epithelial and non-epithelial cellular populations across different tissue developmental stages, mouse strains and mammalian species. Here, we combined differential mammary gland fractionation approaches and transcriptional profiles obtained from FACS-isolated mammary cells to improve our definitions of mammary-resident, cellular identities at the single-cell level. Our approach yielded a series of expression signatures that illustrate the heterogeneity of mammary epithelial cells, specifically those of the luminal fate, and uncovered transcriptional changes to their lineage-defined, cellular states that are induced during gland development. Our analysis also provided molecular signatures that identified non-epithelial mammary cells, including adipocytes, fibroblasts and rare immune cells. Lastly, we extended our study to elucidate expression signatures of human, breast-resident cells, a strategy that allowed for the cross-species comparison of mammary epithelial identities. Collectively, our approach improved the existing signatures of normal mammary epithelial cells, as well as elucidated the diversity of non-epithelial cells in murine and human breast tissue. Our study provides a useful resource for future studies that use single-cell molecular profiling strategies to understand normal and malignant breast development.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"43-66"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09486-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38993529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting the Dots: Mammary Gland and Breast Cancer at Single Cell Resolution.","authors":"Renée van Amerongen,&nbsp;Edith C Kordon,&nbsp;Zuzana Koledova","doi":"10.1007/s10911-021-09492-5","DOIUrl":"https://doi.org/10.1007/s10911-021-09492-5","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"1-2"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09492-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39024556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behind the Scenes of the Human Breast Cell Atlas Project.","authors":"Renée van Amerongen","doi":"10.1007/s10911-021-09482-7","DOIUrl":"10.1007/s10911-021-09482-7","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"67-70"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09482-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38853746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Intravital Microscopy Toolbox to Study Mammary Gland Dynamics from Cellular Level to Organ Scale.","authors":"Hendrik A Messal,&nbsp;Jacco van Rheenen,&nbsp;Colinda L G J Scheele","doi":"10.1007/s10911-021-09487-2","DOIUrl":"https://doi.org/10.1007/s10911-021-09487-2","url":null,"abstract":"<p><p>The architecture of the mouse mammary gland is highly dynamic and constantly remodeled during pubertal development and estrous cycle-driven sprouting and regression of alveolar side branches. During each of these developmental stages, turnover is driven by distinct subsets of mammary epithelial cells. Extensive previous research has shed light on the unique morphological and cell biological characteristics of each stage. However, technological shortcomings failed to capture the dynamics and single-cell contributions to mammary remodeling. Here, we developed in vivo imaging strategies to follow the same mammary ducts over time and quantify the dynamics of mammary gland growth and remodeling from single-cell level to organ scale. Using a combination of intravital microscopy and genetic reporter systems we show how proliferative heterogeneity drives ductal morphogenesis during different developmental stages. To visualize pubertal growth at the cellular level, we performed long-term time-lapse imaging of extending terminal end buds through a mammary imaging window. We show that single-cells within the terminal end buds are extremely motile and continuously exchange position whilst the duct is elongating. To visualize short-term remodeling in the adult mammary gland at the single cell level, we performed multi-day intravital imaging in photoconvertible Kikume Green-Red mice and fluorescent ubiquitination-based cell cycle indicator mice. We demonstrate that the contribution of single-cells to estrous-driven remodeling is highly variable between cells in the same micro-environment. To assess the effects of this dynamic proliferative contribution on the long-term stability of tissue architecture, we developed a repeated skin flap method to assess mammary gland morphology by intravital microscopy over extended time spans for up to six months. Interestingly, in contrast to the short-term dynamic remodeling, the long-term morphology of the mammary gland remains remarkably stable. Together, our tool box of imaging strategies allows to identify and map transient and continuing dynamics of single cells to the architecture of the mammary gland.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"9-27"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09487-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38947056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolving Human Lactation Heterogeneity Using Single Milk-Derived Cells, a Resource at the Ready.","authors":"Jayne F Martin Carli,&nbsp;G Devon Trahan,&nbsp;Michael C Rudolph","doi":"10.1007/s10911-021-09489-0","DOIUrl":"https://doi.org/10.1007/s10911-021-09489-0","url":null,"abstract":"<p><p>Single cell RNA sequencing (scRNAseq) of human milk-derived cells (HMDCs) makes highly detailed analyses of the biology of human lactation possible. We explore this powerful application as an exciting tool to inspect the cellular composition of human milk. We point out some important challenges unique to this approach and highlight the importance of collaborations between biologists and well-trained bioinformaticians to utilize these data to their maximum potential. We extend this focus by discussing the first two such studies that describe HMDCs via scRNAseq and a variety of important questions in the field that warrant attention through further research. The stage is set to apply scRNAseq in human lactation biology, potentially leading to new insights regarding the molecular and cellular diversity of human secretory mammary epithelial cells.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"3-8"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09489-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39070513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to Use Online Tools to Generate New Hypotheses for Mammary Gland Biology Research: A Case Study for Wnt7b.","authors":"Yorick Bernardus Cornelis van de Grift,&nbsp;Nika Heijmans,&nbsp;Renée van Amerongen","doi":"10.1007/s10911-020-09474-z","DOIUrl":"https://doi.org/10.1007/s10911-020-09474-z","url":null,"abstract":"<p><p>An increasing number of '-omics' datasets, generated by labs all across the world, are becoming available. They contain a wealth of data that are largely unexplored. Not every scientist, however, will have access to the required resources and expertise to analyze such data from scratch. Fortunately, a growing number of investigators is dedicating their time and effort to the development of user friendly, online applications that allow researchers to use and investigate these datasets. Here, we will illustrate the usefulness of such an approach. Using regulation of Wnt7b expression as an example, we will highlight a selection of accessible tools and resources that are available to researchers in the area of mammary gland biology. We show how they can be used for in silico analyses of gene regulatory mechanisms, resulting in new hypotheses and providing leads for experimental follow up. We also call out to the mammary gland community to join forces in a coordinated effort to generate and share additional tissue-specific '-omics' datasets and thereby expand the in silico toolbox.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"25 4","pages":"319-335"},"PeriodicalIF":2.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09474-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25400609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Got Milk? Identifying and Characterizing Lactation Defects in Genetically-Engineered Mouse Models.","authors":"Teneale A Stewart,&nbsp;Felicity M Davis","doi":"10.1007/s10911-020-09467-y","DOIUrl":"https://doi.org/10.1007/s10911-020-09467-y","url":null,"abstract":"<p><p>The ability to produce and expel milk is important for the health and survival of all mammals. Nevertheless, our understanding of the molecular events underlying the execution of this process remains incomplete. Whilst impaired mammary gland development and lactational competence remains the subject of focused investigations, defects in these events may also be an unintended consequence of genetic manipulation in rodent models. In this technical report, we outline established and emerging methods to characterize lactation phenotypes in genetically-engineered mouse models. We discuss important considerations of common models, optimized conditions for mating and the importance of litter size and standardization. Methods for quantifying milk production and quality, as well as protocols for wholemount preparation, immunohistochemistry and the preparation of RNA and protein lysates are provided. This review is intended to help guide researchers new to the field of mammary gland biology in the systematic analysis of lactation defects and in the preparation of samples for more focused mechanistic investigations.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"25 4","pages":"255-272"},"PeriodicalIF":2.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09467-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38715436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks.","authors":"Jakub Sumbal,&nbsp;Zuzana Budkova,&nbsp;Gunnhildur Ásta Traustadóttir,&nbsp;Zuzana Koledova","doi":"10.1007/s10911-020-09468-x","DOIUrl":"https://doi.org/10.1007/s10911-020-09468-x","url":null,"abstract":"<p><p>3D cell culture methods have been an integral part of and an essential tool for mammary gland and breast cancer research for half a century. In fact, mammary gland researchers, who discovered and deciphered the instructive role of extracellular matrix (ECM) in mammary epithelial cell functional differentiation and morphogenesis, were the pioneers of the 3D cell culture techniques, including organoid cultures. The last decade has brought a tremendous increase in the 3D cell culture techniques, including modifications and innovations of the existing techniques, novel biomaterials and matrices, new technological approaches, and increase in 3D culture complexity, accompanied by several redefinitions of the terms \"3D cell culture\" and \"organoid\". In this review, we provide an overview of the 3D cell culture and organoid techniques used in mammary gland biology and breast cancer research. We discuss their advantages, shortcomings and current challenges, highlight the recent progress in reconstructing the complex mammary gland microenvironment in vitro and ex vivo, and identify the missing 3D cell cultures, urgently needed to aid our understanding of mammary gland development, function, physiology, and disease, including breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"25 4","pages":"273-288"},"PeriodicalIF":2.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09468-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38714448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo.","authors":"Wen Bu,&nbsp;Yi Li","doi":"10.1007/s10911-020-09469-w","DOIUrl":"https://doi.org/10.1007/s10911-020-09469-w","url":null,"abstract":"<p><p>Various retroviral and lentiviral vectors have been used for up-the-teat intraductal injection to deliver markers, oncogenes, and other genes into mammary epithelial cells in mice. These methods along with the large number of genetically engineered mouse lines have greatly helped us learn normal breast development and tumorigenesis. Rats are also valuable models for studying human breast development and cancer. However, genetically engineered rats are still uncommon, and previous reports of intraductal injection of retroviral vectors into rats appear to be inefficient in generating mammary tumors. Here, we report, and describe the method for, stably introducing marker genes and oncogenes into mammary glands in rats using intraductal injection of commonly used lentiviral vectors. This method can infect mammary epithelial cells efficiently, and the infected cells can initiate tumorigenesis, including estrogen receptor-positive and hormone-dependent tumors, which are the most common subtype of human breast cancer but are yet still difficult to model in mice. This technique provides another tool for studying formation, prevention, and treatment of breast cancer, especially estrogen receptor-positive breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"25 4","pages":"389-396"},"PeriodicalIF":2.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09469-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38589021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools.","authors":"Erin D Giles,&nbsp;Elizabeth A Wellberg","doi":"10.1007/s10911-020-09463-2","DOIUrl":"https://doi.org/10.1007/s10911-020-09463-2","url":null,"abstract":"<p><p>Obesity increases the risk for breast cancer and is associated with poor outcomes for cancer patients. A variety of rodent models have been used to investigate these relationships; however, key differences in experimental approaches, as well as unique aspects of rodent physiology lead to variability in how these valuable models are implemented. We combine expertise in the development and implementation of preclinical models of obesity and breast cancer to disseminate effective practices for studies that integrate these fields. In this review, we share, based on our experience, key considerations for model selection, highlighting important technical nuances and tips for use of preclinical models in studies that integrate obesity with breast cancer risk and progression. We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women's health.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"25 4","pages":"237-253"},"PeriodicalIF":2.5,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09463-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38572616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}