title: Apoptotic caspases regulate induction of iPSCs from human fibroblasts.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Zhimin
authors.initials: Z
authors.lastname: He
authors.forename: Jingping
authors.initials: J
authors.lastname: Shen
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.forename: Wenrong
authors.initials: W
authors.lastname: Li
authors.forename: Xinjian
authors.initials: X
authors.lastname: Liu
authors.forename: Yujun
authors.initials: Y
authors.lastname: He
authors.forename: Frank
authors.initials: F
authors.lastname: Wolf
authors.forename: Chuan-Yuan
authors.initials: CY
authors.lastname: Li
mesh_terms: 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
chemical_list: D053148:Caspase 3; D053181:Caspase 8