title: Generating trunk neural crest from human pluripotent stem cells.
abstract: Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior "cranial" NCC form craniofacial bone, whereas solely posterior "trunk" NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages.
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.
authors.forename: Miller
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Miller
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: McHenry
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Zhen
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.
authors.forename: Shirin
authors.initials: S
authors.lastname: Ilkhanizadeh
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158 USA.|Departments of Medicine and Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Conklin
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
authors.affiliation: Department of Neurology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 USA.|Departments of Pediatrics, Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, CA 94158 USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Weiss
mesh_terms: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D014212:Tretinoin
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