دورية أكاديمية
Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures.
العنوان: | Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. |
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المؤلفون: | Chou BK; Stem Cell Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Mali P, Huang X, Ye Z, Dowey SN, Resar LM, Zou C, Zhang YA, Tong J, Cheng L |
المصدر: | Cell research [Cell Res] 2011 Mar; Vol. 21 (3), pp. 518-29. Date of Electronic Publication: 2011 Jan 18. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9425763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1748-7838 (Electronic) Linking ISSN: 10010602 NLM ISO Abbreviation: Cell Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke, England : Nature Publishing Group Original Publication: Beijing, China : Science Press, 1990- |
مواضيع طبية MeSH: | Epigenesis, Genetic* , Gene Expression Profiling*, Blood Cells/*cytology , Induced Pluripotent Stem Cells/*metabolism , Plasmids/*metabolism, Antigens, CD34/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cellular Reprogramming ; Fetal Blood/cytology ; Fibroblasts/cytology ; Hematopoietic Stem Cells/metabolism ; Humans ; Plasmids/genetics ; RNA-Binding Proteins |
مستخلص: | To identify accessible and permissive human cell types for efficient derivation of induced pluripotent stem cells (iPSCs), we investigated epigenetic and gene expression signatures of multiple postnatal cell types such as fibroblasts and blood cells. Our analysis suggested that newborn cord blood (CB) and adult peripheral blood (PB) mononuclear cells (MNCs) display unique signatures that are closer to iPSCs and human embryonic stem cells (ESCs) than age-matched fibroblasts to iPSCs/ESCs, thus making blood MNCs an attractive cell choice for the generation of integration-free iPSCs. Using an improved EBNA1/OriP plasmid expressing 5 reprogramming factors, we demonstrated highly efficient reprogramming of briefly cultured blood MNCs. Within 14 days of one-time transfection by one plasmid, up to 1000 iPSC-like colonies per 2 million transfected CB MNCs were generated. The efficiency of deriving iPSCs from adult PB MNCs was approximately 50-fold lower, but could be enhanced by inclusion of a second EBNA1/OriP plasmid for transient expression of additional genes such as SV40 T antigen. The duration of obtaining bona fide iPSC colonies from adult PB MNCs was reduced to half (∼14 days) as compared to adult fibroblastic cells (28-30 days). More than 9 human iPSC lines derived from PB or CB blood cells are extensively characterized, including those from PB MNCs of an adult patient with sickle cell disease. They lack V(D)J DNA rearrangements and vector DNA after expansion for 10-12 passages. This facile method of generating integration-free human iPSCs from blood MNCs will accelerate their use in both research and future clinical applications. |
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معلومات مُعتمدة: | RC2 HL101582 United States HL NHLBI NIH HHS; T32 HL007525 United States HL NHLBI NIH HHS; U01 HL099775 United States HL NHLBI NIH HHS; R01 HL073781 United States HL NHLBI NIH HHS; T32HL007525 United States HL NHLBI NIH HHS; U01HL099775 United States HL NHLBI NIH HHS; R01HL073781 United States HL NHLBI NIH HHS; RC2HL101582 United States HL NHLBI NIH HHS |
المشرفين على المادة: | 0 (Antigens, CD34) 0 (Carrier Proteins) 0 (EBNA1BP2 protein, human) 0 (RNA-Binding Proteins) |
تواريخ الأحداث: | Date Created: 20110119 Date Completed: 20110620 Latest Revision: 20211020 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC3193421 |
DOI: | 10.1038/cr.2011.12 |
PMID: | 21243013 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1748-7838 |
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DOI: | 10.1038/cr.2011.12 |