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Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program.
Kanchan, Kanika; Iyer, Kruthika; Yanek, Lisa R; Carcamo-Orive, Ivan; Taub, Margaret A; Malley, Claire; Baldwin, Kristin; Becker, Lewis C; Broeckel, Ulrich; Cheng, Linzhao; Cowan, Chad; D'Antonio, Matteo; Frazer, Kelly A; Quertermous, Thomas; Mostoslavsky, Gustavo; Murphy, George; Rabinovitch, Marlene; Rader, Daniel J; Steinberg, Martin H; Topol, Eric; Yang, Wenli; Knowles, Joshua W; Jaquish, Cashell E; Ruczinski, Ingo; Mathias, Rasika A.
Afiliação
  • Kanchan K; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Iyer K; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Yanek LR; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Carcamo-Orive I; Department of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
  • Taub MA; Department of Biostatistics, Bloomberg School of Public health, Johns Hopkins University, Baltimore, MD, USA.
  • Malley C; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Baldwin K; Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Becker LC; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Broeckel U; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Cheng L; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Cowan C; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • D'Antonio M; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
  • Frazer KA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
  • Quertermous T; Department of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
  • Mostoslavsky G; The Center for Regenerative Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
  • Murphy G; The Center for Regenerative Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
  • Rabinovitch M; Department of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
  • Rader DJ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Steinberg MH; Department of Medicine, Section of Hematology-Oncology, Boston University School of Medicine, Boston, MA, USA.
  • Topol E; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
  • Yang W; Penn Center for Pulmonary Biology and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Knowles JW; Department of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
  • Jaquish CE; National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
  • Ruczinski I; Department of Biostatistics, Bloomberg School of Public health, Johns Hopkins University, Baltimore, MD, USA.
  • Mathias RA; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Stem Cell Res ; 46: 101803, 2020 07.
Article em En | MEDLINE | ID: mdl-32442913
ABSTRACT
Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes Induzidas Limite: Humans País/Região como assunto: America do norte Idioma: En Revista: Stem Cell Res Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Células-Tronco Pluripotentes Induzidas Limite: Humans País/Região como assunto: America do norte Idioma: En Revista: Stem Cell Res Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos