title: Induced pluripotent stem cells: a novel frontier in the study of human primary immunodeficiencies.
abstract: BACKGROUND
  The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells (iPSCs) through the exogenous expression of transcription promises to revolutionize the study of human diseases.
  
  
  OBJECTIVE
  Here we report on the generation of 25 iPSC lines from 6 patients with various forms of primary immunodeficiencies (PIDs) affecting adaptive immunity, innate immunity, or both.
  
  
  METHODS
  Patients' dermal fibroblasts were reprogrammed by expression of 4 transcription factors, octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), Krueppel-like factor 4 (KLF4), and cellular myelomonocytosis proto-oncogene (cMYC), by using a single excisable polycistronic lentiviral vector.
  
  
  RESULTS
  iPSCs derived from patients with PIDs show a stemness profile that is comparable with that observed in human embryonic stem cells. After in vitro differentiation into embryoid bodies, pluripotency of the patient-derived iPSC lines was demonstrated by expression of genes characteristic of each of the 3 embryonic layers. We have confirmed the patient-specific origin of the iPSC lines and ascertained maintenance of karyotypic integrity.
  
  
  CONCLUSIONS
  By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of iPSC lines from patients with PIDs represents a unique resource to investigate the pathophysiology of hematopoietic and extrahematopoietic manifestations of these diseases and might assist in the development of novel therapeutic approaches based on gene correction.
authors.affiliation: Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Itai M
authors.initials: IM
authors.lastname: Pessach
authors.forename: Jose
authors.initials: J
authors.lastname: Ordovas-Montanes
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Silvia
authors.initials: S
authors.lastname: Giliani
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Herz
authors.forename: Philip D
authors.initials: PD
authors.lastname: Manos
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Schlaeger
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.forename: Francesca
authors.initials: F
authors.lastname: Rucci
authors.forename: Suneet
authors.initials: S
authors.lastname: Agarwal
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mostoslavsky
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D056704:Adaptive Immunity; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D002460:Cell Line; D054338:Cell Transdifferentiation; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D057026:Induced Pluripotent Stem Cells / Q000473:pathology* / Q000502:physiology*; D007621:Karyotyping; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D000090063:Proto-Oncogene Mas; D055748:SOXB1 Transcription Factors / Q000235:genetics
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C000715470:MAS1 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D000090063:Proto-Oncogene Mas; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D004247:DNA