title: Generation of disease-specific induced pluripotent stem cells from patients with different karyotypes of Down syndrome.
abstract: BACKGROUND
  Down syndrome (DS), a major cause of mental retardation, is caused by trisomy of some or all of human chromosome 21 and includes three basic karyotypes: trisomy 21, translocation, and mosaicism. The derivation of DS-specific induced pluripotent stem cells (iPSCs) provides us novel DS models that can be used to determine the DS mechanism and to devise therapeutic approaches for DS patients.
  
  
  METHODS
  In the present study, fibroblasts from patients with DS of various karyotypes were reprogrammed into iPSCs via the overexpression of four factors: OCT4, SOX2, KLF4, and c-MYC, by using lentiviral vectors. The abilities of the iPSC-DS in the self-renewal and pluripotency in vitro and in vivo were then examined.
  
  
  RESULTS
  The iPSC-DS showed characteristics similar to those of human embryonic stem cells, particularly the morphology, surface marker (SSEA4, TRA-1-60, and TRA-1-81) expression, pluripotent-specific transcription-factor expression levels, and methylation status of the OCT4 promoter. The pluripotency of iPSC-DS was also tested in vitro and in vivo. Embryoid bodies were formed and showed the expression of differentiated markers for three germ layers. Furthermore, iPSC-DS formed classic teratomas when injected into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice.
  
  
  CONCLUSIONS
  iPSCs were generated from patients with DS. The iPSCs derived from different types of DS may be used in DS modeling, patient-care optimization, drug discovery, and eventually, autologous cell-replacement therapies.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Mou
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Wu
authors.forename: Henghua
authors.initials: H
authors.lastname: Cao
authors.forename: Qingzhang
authors.initials: Q
authors.lastname: Meng
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wang
authors.forename: Chengchao
authors.initials: C
authors.lastname: Sun
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D059786:Abnormal Karyotype; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002675:Child, Preschool; D004314:Down Syndrome / Q000235:genetics* / Q000628:therapy; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013724:Teratoma
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors