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A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells.

TitleA murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells.
Publication TypeJournal Article
Year of Publication2010
AuthorsBuecker C, Chen H-H, Polo JMaria, Daheron L, Bu L, Barakat TStefan, Okwieka P, Porter A, Gribnau J, Hochedlinger K, Geijsen N
JournalCell Stem Cell
Volume6
Issue6
Pagination535-46
Date Published2010 Jun 4
ISSN1875-9777
KeywordsAnimals, Antigens, Differentiation, Cell Dedifferentiation, Cell Line, Embryonic Stem Cells, Fibroblast Growth Factor 2, Gene Transfer Techniques, Genetic Therapy, Humans, Induced Pluripotent Stem Cells, Leukemia Inhibitory Factor, Mice, Recombination, Genetic, Sequence Homology, Transcription Factors
Abstract

Murine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human iPSC reprogramming in the presence of LIF yields human stem cells that display morphological, molecular, and functional properties of murine ESCs. We termed these hLR5 iPSCs because they require the expression of five ectopic reprogramming factors, Oct4, Sox2, Klf4, cMyc, and Nanog, to maintain this more naive state. The cells are "metastable" and upon ectopic factor withdrawal they revert to standard human iPSCs. Finally, we demonstrate that the hLR5 state facilitates gene targeting, and as such provides a powerful tool for the generation of recombinant human pluripotent stem cell lines.

DOI10.1016/j.stem.2010.05.003
Alternate JournalCell Stem Cell
PubMed ID20569691
PubMed Central IDPMC3162213
Grant ListR01 HD048769 / HD / NICHD NIH HHS / United States
R01 HD048769-03 / HD / NICHD NIH HHS / United States
R01 HD048769-03S1 / HD / NICHD NIH HHS / United States
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