title: Differentiation of Human Induced Pluripotent Stem Cells to Mammary-like Organoids.
abstract: Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease-modeling applications. We have developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm-cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-day differentiated mEBs. We then generated mammary-like organoids from 10-day mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation. Our findings provide an iPSC-based model for studying regulation of normal mammary cell fate and function as well as breast disease development.
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis Building 2065, Los Angeles, CA 90048, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis Building 2065, Los Angeles, CA 90048, USA.
authors.forename: Bingchen
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis Building 2065, Los Angeles, CA 90048, USA.
authors.forename: Bowen
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Pathology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.affiliation: Department of Breast Surgery, Hubei Cancer Hospital, Wuhan 430079, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Kolja
authors.initials: K
authors.lastname: Wawrowsky
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis Building 2065, Los Angeles, CA 90048, USA.
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; The David and Janet Polak Foundation Stem Cell Core Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Sareen
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis Building 2065, Los Angeles, CA 90048, USA. Electronic address: xiaojiang.cui@cshs.org.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
mesh_terms: D015415:Biomarkers; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D004475:Ectoderm / Q000166:cytology / Q000196:embryology; D058732:Embryoid Bodies / Q000166:cytology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009940:Organoids / Q000166:cytology; D044968:Regenerative Medicine; D059467:Transcriptome
chemical_list: D015415:Biomarkers
keywords: 3D culture; alveolar structure; ectoderm; iPSC; mammary-like cells; organoid