Reprogramming of pancreatic β cells into induced pluripotent stem cells

被引:362
作者
Stadtfeld, Matthias [1 ,2 ,3 ]
Brennand, Kristen [3 ,4 ,5 ]
Hochedlinger, Konrad [1 ,2 ,3 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA
[3] Harvard Stem Cell Inst, Cambridge, MA 02138 USA
[4] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA
[5] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
关键词
D O I
10.1016/j.cub.2008.05.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Induced pluripotent stem (iPS) cells have been derived from fibroblast, stomach, and liver cultures at extremely low frequencies by ectopic expression of the transcription factors Oct4, Sox2, c-myc, and KIM, a process coined direct or in vitro reprogramming [1-8]. iPS cells are molecularly and functionally highly similar to embryonic stem cells (ESCs), including their ability to contribute to all tissues as well as the germline in mice. The heterogeneity of the starting cell populations and the low efficiency of reprogramming suggested that a rare cell type, such as an adult stem cell, might be the cell of origin for iPS cells and that differentiated cells are refractory to reprogramming. Here, we used inducible lentiviruses [9] to express Oct4, Sox2, c-myc, and KIM in pancreatic beta cells to assess whether a defined terminally differentiated cell type remains amenable to reprogramming. Genetically marked beta cells gave rise to iPS cells that expressed pluripotency markers, formed teratomas, and contributed to cell types of all germ layers in chimeric animals. Our results provide genetic proof that terminally differentiated cells can be reprogrammed into pluripotent cells, suggesting that in vitro reprogramming is not restricted to certain cell types or differentiation stages.
引用
收藏
页码:890 / 894
页数:5
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