title: Transcriptome and proteome characterization of surface ectoderm cells differentiated from human iPSCs.
abstract: Surface ectoderm (SE) cells give rise to structures including the epidermis and ectodermal associated appendages such as hair, eye, and the mammary gland. In this study, we validate a protocol that utilizes BMP4 and the γ-secretase inhibitor DAPT to induce SE differentiation from human induced pluripotent stem cells (hiPSCs). hiPSC-differentiated SE cells expressed markers suggesting their commitment to the SE lineage. Computational analyses using integrated quantitative transcriptomic and proteomic profiling reveal that TGFβ superfamily signaling pathways are preferentially activated in SE cells compared with hiPSCs. SE differentiation can be enhanced by selectively blocking TGFβ-RI signaling. We also show that SE cells and neural ectoderm cells possess distinct gene expression patterns and signaling networks as indicated by functional Ingenuity Pathway Analysis. Our findings advance current understanding of early human SE cell development and pave the way for modeling of SE-derived tissue development, studying disease pathogenesis, and development of regenerative medicine approaches.
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Bingchen
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu-Rice
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Bowen
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Board of Governors-Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Freeman
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.affiliation: Board of Governors-Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.|iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Los Angeles, CA, 90048, USA.|Department of Biomedical Sciences, 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, Los Angeles, CA, 90048, USA.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003959:Diamines / Q000494:pharmacology*; D004475:Ectoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C000612000:24-diamino-5-phenylthiazole; D055415:Bone Morphogenetic Protein 4; D003959:Diamines; D013844:Thiazoles; D016212:Transforming Growth Factor beta