Journal ArticleDOI
Reprogramming of human somatic cells to pluripotency with defined factors
In-Hyun Park,In-Hyun Park,Rui Zhao,Rui Zhao,Jason A. West,Jason A. West,Akiko Yabuuchi,Akiko Yabuuchi,Hongguang Huo,Hongguang Huo,Tan A. Ince,Paul H. Lerou,M. William Lensch,M. William Lensch,George Q. Daley,George Q. Daley +15 more
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TLDR
The data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.Abstract:
Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.read more
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Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Stuart M. Chambers,Christopher A. Fasano,Eirini P. Papapetrou,Mark J. Tomishima,Michel Sadelain,Lorenz Studer +5 more
TL;DR: Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.
Journal ArticleDOI
Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA
Luigi Warren,Philip D. Manos,Philip D. Manos,Tim Ahfeldt,Tim Ahfeldt,Yuin-Han Loh,Hu Li,Hu Li,Frank H. Lau,Wataru Ebina,Pankaj Mandal,Zachary D. Smith,Alexander Meissner,Alexander Meissner,George Q. Daley,Andrew S. Brack,James J. Collins,James J. Collins,James J. Collins,Chad A. Cowan,Thorsten M. Schlaeger,Thorsten M. Schlaeger,Derrick J. Rossi +22 more
TL;DR: It is shown that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols and represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.
Journal ArticleDOI
Growth Factors, Matrices, and Forces Combine and Control Stem Cells
TL;DR: Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.
Journal ArticleDOI
Disease-Specific Induced Pluripotent Stem Cells
In-Hyun Park,Natasha Arora,Hongguang Huo,Nimet Maherali,Tim Ahfeldt,Tim Ahfeldt,Akiko Shimamura,M. William Lensch,M. William Lensch,Chad A. Cowan,Konrad Hochedlinger,George Q. Daley +11 more
TL;DR: The generation of induced pluripotent stem cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance are described, offering an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.
Journal ArticleDOI
Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors
TL;DR: The production of virus-free iPS cells, albeit from embryonic fibroblasts, addresses a critical safety concern for potential use of i PS cells in regenerative medicine.
References
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Journal ArticleDOI
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
Journal ArticleDOI
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
Journal ArticleDOI
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Junying Yu,Maxim A. Vodyanik,Kim Smuga-Otto,Jessica Antosiewicz-Bourget,Jennifer L. Frane,Shulan Tian,Jeff Nie,Gudrun A. Jonsdottir,Victor Ruotti,Ron Stewart,Igor I. Slukvin,James A. Thomson +11 more
TL;DR: This article showed that OCT4, SOX2, NANOG, and LIN28 factors are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells.
Journal ArticleDOI
Extension of life-span by introduction of telomerase into normal human cells
Andrea G. Bodnar,Michel M. Ouellette,Maria Frolkis,Shawn E. Holt,Choy-Pik Chiu,Gregg B. Morin,Calvin B. Harley,Jerry W. Shay,Serge Lichtsteiner,Woodring E. Wright +9 more
TL;DR: In this article, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomere catalytic subunit.
Journal ArticleDOI
Generation of germline-competent induced pluripotent stem cells
TL;DR: iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.