Trisomy 21 mid-trimester amniotic fluid induced pluripotent stem cells maintain genetic signatures during reprogramming: Implications for disease modeling and cryobanking


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Pipino, C. and Mukherjee, S. and David, A.L. and Blundell, M.P. and Shaw, S.W. and Sung, P. and Shangaris, P. and Waters, J.J. and Ellershaw, D. and Cavazzana, M. and Mostoslavsky, G.l and Pandolfi, A. and Pierro, A. and Guillot, P.V. and Thrasher, A.J. and De Coppi, P. (2014) Trisomy 21 mid-trimester amniotic fluid induced pluripotent stem cells maintain genetic signatures during reprogramming: Implications for disease modeling and cryobanking. Cellular Reprogramming, 16 (5). pp. 331-344. ISSN 21524971

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Trisomy 21 is the most common chromosomal abnormality and is associated primarily with cardiovascular, hematological, and neurological complications. A robust patient-derived cellular model is necessary to investigate the pathophysiology of the syndrome because current animal models are limited and access to tissues from affected individuals is ethically challenging. We aimed to derive induced pluripotent stem cells (iPSCs) from trisomy 21 human mid-trimester amniotic fluid stem cells (AFSCs) and describe their hematopoietic and neurological characteristics. Human AFSCs collected from women undergoing prenatal diagnosis were selected for c-KIT+and transduced with a Cre-lox-inducible polycistronic lentiviral vector encoding SOX2, OCT4, KLF-4, and c-MYC (50,000 cells at a multiplicity of infection (MOI) 1-5 for 72h). The embryonic stem cell (ESC)-like properties of the AFSC-derived iPSCs were established in vitro by embryoid body formation and in vivo by teratoma formation in RAG2-/-, γ-chain-/-, C2-/-immunodeficient mice. Reprogrammed cells retained their cytogenetic signatures and differentiated into specialized hematopoietic and neural precursors detected by morphological assessment, immunostaining, and RT-PCR. Additionally, the iPSCs expressed all pluripotency markers upon multiple rounds of freeze-thawing. These findings are important in establishing a patient-specific cellular platform of trisomy 21 to study the pathophysiology of the aneuploidy and for future drug discovery. © 2014 Mary Ann Liebert, Inc.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: kruppel like factor 4; lentivirus vector; Myc protein; octamer transcription factor 4; RAG2 protein; transcription factor Sox2, amnion fluid; amniotic fluid cell; amniotic fluid stem cell; animal model; animal tissue; Article; carcinogenesis; cell differentiation; cell structure; controlled study; cryopreservation; cytogenetics; disease model; embryo development; embryoid body; embryonic stem cell; female; fetus; freeze thawing; hematopoietic stem cell; human; human cell; immunohistochemistry; in vitro study; in vivo study; mouse; neural stem cell; nonhuman; nuclear reprogramming; pluripotent stem cell; pregnant woman; prenatal diagnosis; protein expression; protein structure; reverse transcription polymerase chain reaction; second trimester pregnancy; teratoma; trisomy 21; animal; biological model; cryopreservation; cytology; Down syndrome; pluripotent stem cell; pregnancy, Amniotic Fluid; Animals; Cryopreservation; Down Syndrome; Female; Humans; Induced Pluripotent Stem Cells; Mice; Models, Biological; Pregnancy; Prenatal Diagnosis
Subjects: Faculty of Science > Environmental and Biological Sciences > Biological Sciences
Divisions: Jnana Bharathi / Central College Campus > Department of Biological Sciences
Depositing User: Mr. Kirana Kumar D
Date Deposited: 13 Apr 2016 07:04
Last Modified: 13 Apr 2016 07:04

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