Apoptotic caspases regulate induction of iPSCs from human fibroblasts.
The molecular mechanisms involved in the derivation of induced pluripotent stem cells (iPSCs) from differentiated cells are poorly understood. Here we report that caspases 3 and 8, two proteases associated with apoptotic cell death, play critical roles in induction of iPSCs from human fibroblasts. Activation of caspases 3 and 8 occurs soon after transduction of iPSC-inducing transcription factors. Oct-4, a key iPSC transcription factor, is responsible for the activation. Inhibition of caspase 3 or 8 in human fibroblast cells partially or completely (respectively) prevents the induction of iPSCs. Furthermore, retinoblastoma susceptibility (Rb) protein appears to be one of the factors that act downstream of the caspases. We propose that caspases are key facilitators of nuclear reprogramming in iPSC induction.
Li
Fang
F
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
He
Zhimin
Z
Shen
Jingping
J
Huang
Qian
Q
Li
Wenrong
W
Liu
Xinjian
X
He
Yujun
Y
Wolf
Frank
F
Li
Chuan-Yuan
CY
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells
D053148:Caspase 3; D053181:Caspase 8