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. A...

Full description

Saved in:
Bibliographic Details
Published inCell stem cell Vol. 7; no. 4; pp. 508 - 520
Main Authors Li, Fang, He, Zhimin, Shen, Jingping, Huang, Qian, Li, Wenrong, Liu, Xinjian, He, Yujun, Wolf, Frank, Li, Chuan-Yuan
Format Journal Article
LanguageEnglish
Published Cambridge, MA Elsevier Inc 08.10.2010
Cell Press
Subjects
Ageing, cell death
Apoptosis
Biological and medical sciences
Caspase 3 - metabolism
Caspase 8 - metabolism
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
Cellular Reprogramming
Fibroblasts - cytology
Fibroblasts - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Induced Pluripotent Stem Cells
Molecular and cellular biology
Human
Peptidases
Regulation(control)
Enzyme
Induction
Caspase
Hydrolases
Fibroblast
Apoptosis
Online AccessGet full text

Cover

More Information
Summary: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. [Display omitted] ► Caspases 3 and 8 are activated in iPSC induction ► Transduction of Oct-4 alone is sufficient to activate caspases 3 and 8 ► Inhibition of caspase 3 and 8 activation significantly impedes iPSC induction ► Retinoblastoma protein (Rb) acts downstream of caspases 3 and 8 in iPSC induction
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2010.09.003