Generation of pluripotent stem cells from patients with type 1 diabetes

被引:409
作者
Maehr, Rene [1 ]
Chen, Shuibing [1 ]
Snitow, Melinda [1 ]
Ludwig, Thomas [2 ]
Yagasaki, Lisa [1 ]
Goland, Robin [3 ,4 ]
Leibel, Rudolph L. [3 ,4 ]
Melton, Douglas A. [1 ]
机构
[1] Harvard Univ, Harvard Stem Cell Inst, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, Div Mol Genet, New York, NY 10032 USA
[4] Columbia Univ, Coll Phys & Surg, Naomi Barrie Diabet Ctr, New York, NY 10032 USA
关键词
beta cell; disease model; autoimmune; directed differentiation; endoderm; HUMAN FIBROBLASTS; ANIMAL-MODELS; MOUSE; DIFFERENTIATION; INDUCTION; ENDODERM; LINES;
D O I
10.1073/pnas.0906894106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic beta cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.
引用
收藏
页码:15768 / 15773
页数:6
相关论文
共 29 条
[1]   A small molecule that directs differentiation of human ESCs into the pancreatic lineage [J].
Chen, Shuibing ;
Borowiak, Malgorzata ;
Fox, Julia L. ;
Maehr, Rene ;
Osafune, Kenji ;
Davidow, Lance ;
Lam, Kelvin ;
Peng, Lee F. ;
Schreiber, Stuart L. ;
Rubin, Lee L. ;
Melton, Douglas .
NATURE CHEMICAL BIOLOGY, 2009, 5 (04) :258-265
[2]  
Cowan CA, 2004, NEW ENGL J MED, V350, P1353, DOI 10.1056/NEJMsr040330
[3]   Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells [J].
D'Amour, Kevin A. ;
Bang, Anne G. ;
Eliazer, Susan ;
Kelly, Olivia G. ;
Agulnick, Alan D. ;
Smart, Nora G. ;
Moorman, Mark A. ;
Kroon, Evert ;
Carpenter, Melissa K. ;
Baetge, Emmanuel E. .
NATURE BIOTECHNOLOGY, 2006, 24 (11) :1392-1401
[4]   Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 [J].
Danwei Huangfu ;
Osafune, Kenji ;
Maehr, Rene ;
Guo, Wenjun ;
Eijkelenboom, Astrid ;
Chen, Shuibing ;
Muhlestein, Whitney ;
Melton, Douglas A. .
NATURE BIOTECHNOLOGY, 2008, 26 (11) :1269-1275
[5]   Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons [J].
Dimos, John T. ;
Rodolfa, Kit T. ;
Niakan, Kathy K. ;
Weisenthal, Laurin M. ;
Mitsumoto, Hiroshi ;
Chung, Wendy ;
Croft, Gist F. ;
Saphier, Genevieve ;
Leibel, Rudy ;
Goland, Robin ;
Wichterle, Hynek ;
Henderson, Christopher E. ;
Eggan, Kevin .
SCIENCE, 2008, 321 (5893) :1218-1221
[6]   Induced pluripotent stem cells from a spinal muscular atrophy patient [J].
Ebert, Allison D. ;
Yu, Junying ;
Rose, Ferrill F., Jr. ;
Mattis, Virginia B. ;
Lorson, Christian L. ;
Thomson, James A. ;
Svendsen, Clive N. .
NATURE, 2009, 457 (7227) :277-U1
[7]   Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo [J].
Kroon, Evert ;
Martinson, Laura A. ;
Kadoya, Kuniko ;
Bang, Anne G. ;
Kelly, Olivia G. ;
Eliazer, Susan ;
Young, Holly ;
Richardson, Mike ;
Smart, Nora G. ;
Cunningham, Justine ;
Agulnick, Alan D. ;
D'Amour, Kevin A. ;
Carpenter, Melissa K. ;
Baetge, Emmanuel E. .
NATURE BIOTECHNOLOGY, 2008, 26 (04) :443-452
[8]  
Lakey JRT, 2006, METH MOL B, V333, P47
[9]   Generation of human induced pluripotent stem cells from dermal fibroblasts [J].
Lowry, W. E. ;
Richter, L. ;
Yachechko, R. ;
Pyle, A. D. ;
Tchieu, J. ;
Sridharan, R. ;
Clark, A. T. ;
Plath, K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :2883-2888
[10]  
MONAGHAN AP, 1993, DEVELOPMENT, V119, P567