title: Derivation of induced pluripotent stem cells from orangutan skin fibroblasts.
abstract: BACKGROUND
  Orangutans are an endangered species whose natural habitats are restricted to the Southeast Asian islands of Borneo and Sumatra. Along with the African great apes, orangutans are among the closest living relatives to humans. For potential species conservation and functional genomics studies, we derived induced pluripotent stem cells (iPSCs) from cryopreserved somatic cells obtained from captive orangutans.
  
  
  RESULTS
  Primary skin fibroblasts from two Sumatran orangutans were transduced with retroviral vectors expressing the human OCT4, SOX2, KLF4, and c-MYC factors. Candidate orangutan iPSCs were characterized by global gene expression and DNA copy number analysis. All were consistent with pluripotency and provided no evidence of large genomic insertions or deletions. In addition, orangutan iPSCs were capable of producing cells derived from all three germ layers in vitro through embryoid body differentiation assays and in vivo through teratoma formation in immune-compromised mice.
  
  
  CONCLUSIONS
  We demonstrate that orangutan skin fibroblasts are capable of being reprogrammed into iPSCs with hallmark molecular signatures and differentiation potential. We suggest that reprogramming orangutan somatic cells in genome resource banks could provide new opportunities for advancing assisted reproductive technologies relevant for species conservation efforts. Furthermore, orangutan iPSCs could have applications for investigating the phenotypic relevance of genomic changes that occurred in the human, African great ape, and/or orangutan lineages. This provides opportunities for orangutan cell culture models that would otherwise be impossible to develop from living donors due to the invasive nature of the procedures required for obtaining primary cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA. krishnaramaswamy@gmail.com.
authors.forename: Krishna
authors.initials: K
authors.lastname: Ramaswamy
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA. winnie.yik@gmail.com.
authors.forename: Wing Yan
authors.initials: WY
authors.lastname: Yik
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA. xiaomingwangusc@gmail.com.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA. enoliphant@gmail.com.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Oliphant
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA. wangelu@usc.edu.
authors.forename: Wange
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. dshibata@usc.edu.
authors.forename: Darryl
authors.initials: D
authors.lastname: Shibata
authors.affiliation: San Diego Zoo Institute for Conservation Research , San Diego Zoo Global, San Diego, CA, USA. ryder@ucsd.edu.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Ryder
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA. hacia@hsc.usc.edu.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Hacia
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming / Q000235:genetics*; D015925:Cryopreservation; D056915:DNA Copy Number Variations; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D057079:Pongo / Q000235:genetics*; D061251:Primary Cell Culture; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors