Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes

被引:998
作者
Aasen, Trond [1 ,3 ]
Raya, Angel [1 ,2 ,3 ]
Barrero, Maria J. [1 ]
Garreta, Elena [1 ,3 ]
Consiglio, Antonella [1 ,4 ]
Gonzalez, Federico [1 ,5 ]
Vassena, Rita [1 ]
Bilic, Josipa [1 ]
Pekarik, Vladimir [1 ]
Tiscornia, Gustavo [1 ]
Edel, Michael [1 ]
Boue, Stephanie [1 ,3 ]
Izpisua Belmonte, Juan Carlos [1 ,5 ]
机构
[1] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain
[2] Univ Brescia, ICREA, I-25123 Brescia, Italy
[3] Univ Brescia, Networking Ctr Biomed Res Bioengn Biomat & Nanome, I-25123 Brescia, Italy
[4] Univ Brescia, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy
[5] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA
基金
瑞士国家科学基金会;
关键词
D O I
10.1038/nbt.1503
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The utility of induced pluripotent stem (iPS) cells for investigating the molecular logic of pluripotency and for eventual clinical application is limited by the low efficiency of current methods for reprogramming. Here we show that reprogramming of juvenile human primary keratinocytes by retroviral transduction with OCT4, SOX2, KLF4 and c-MYC is at least 100-fold more efficient and twofold faster compared with reprogramming of human fibroblasts. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, global gene expression profiles and differentiation potential in vitro and in vivo. To underscore the efficiency and practicability of this technology, we generated KiPS cells from single adult human hairs. Our findings provide an experimental model for investigating the bases of cellular reprogramming and highlight potential advantages of using keratinocytes to generate patient-specific iPS cells.
引用
收藏
页码:1276 / 1284
页数:9
相关论文
共 30 条
[1]   Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons [J].
Amoh, Y ;
Li, L ;
Katsuoka, K ;
Penman, S ;
Hoffman, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (15) :5530-5534
[2]   Generation of pluripotent stem cells from adult mouse liver and stomach cells [J].
Aoi, Takashi ;
Yae, Kojiro ;
Nakagawa, Masato ;
Ichisaka, Tomoko ;
Okita, Keisuke ;
Takahashi, Kazutoshi ;
Chiba, Tsutomu ;
Yamanaka, Shinya .
SCIENCE, 2008, 321 (5889) :699-702
[3]   A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas [J].
Assou, Said ;
Le Carrour, Tanguy ;
Tondeur, Sylvie ;
Strom, Susanne ;
Gabelle, Audrey ;
Marty, Sophie ;
Nadal, Laure ;
Pantesco, Veronique ;
Reme, Thierry ;
Hugnot, Jean-Philippe ;
Gasca, Stephan ;
Hovatta, Outi ;
Hamamah, Samir ;
Klein, Bernard ;
De Vos, John .
STEM CELLS, 2007, 25 (04) :961-973
[4]   Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells [J].
Brambrink, Tobias ;
Foreman, Ruth ;
Welstead, G. Grant ;
Lengner, Christopher J. ;
Wernig, Marius ;
Suh, Heikyung ;
Jaenisch, Rudolf .
CELL STEM CELL, 2008, 2 (02) :151-159
[5]   Open source clustering software [J].
de Hoon, MJL ;
Imoto, S ;
Nolan, J ;
Miyano, S .
BIOINFORMATICS, 2004, 20 (09) :1453-1454
[6]   Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells [J].
Draper, JS ;
Smith, K ;
Gokhale, P ;
Moore, HD ;
Maltby, E ;
Johnson, J ;
Meisner, L ;
Zwaka, TP ;
Thomson, JA ;
Andrews, PW .
NATURE BIOTECHNOLOGY, 2004, 22 (01) :53-54
[7]   Epigenetic reprogramming of OCT4 and NANOG regulatory regions by embryonal carcinoma cell extract [J].
Freberg, Christel T. ;
Dahl, John Arne ;
Timoskainen, Sanna ;
Collas, Philippe .
MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (05) :1543-1553
[8]   Scratching the surface of skin development [J].
Fuchs, Elaine .
NATURE, 2007, 445 (7130) :834-842
[9]   c-Myc promotes differentiation of human epidermal stem cells [J].
Gandarillas, A ;
Watt, FM .
GENES & DEVELOPMENT, 1997, 11 (21) :2869-2882
[10]  
HAWLEY RG, 1994, GENE THER, V1, P136