The role of CIIA gene in cellular reprogramming

Abstract

Terminally differentiated cells are known to be reprogrammed into induced pluripotent stem cells (iPSCs) when Yamanaka factors (Oct4, Sox2, klf4 and cmyc; OSKM) are introduced. In recent years, iPSC technology has been applied to improve the efficiency and safety of clinical applications. This study demonstrates that knockdown of the CIIA gene (a caspase-activated DNase inhibitor that interacts with ASK1) can enhance reprogramming efficiency in human fibroblasts. Short-term repression of CIIA by siRNA transfection in fibroblasts reduced epithelial-mesenchymal transition (EMT) in the early stage of reprogramming. On the other hand, prolonged suppression of CIIA through shRNA knocking-down induced epigenetic modifiers and pluripotent genes in the late stage of cellular reprogramming. At the transcriptional level, CIIA also acts as an inhibitory influence on the reprogramming process through a histone modification factor, Sirt1. In addition, fibroblasts via knocking-down of CIIA and transfection of OSKM produced greater numbers of embryonic stem cell (ESC)？like colonies, compared with those with OSKM transfection alone. Collectively, these results show that the CIIA gene plays a role in cell fate change and provide a new mechanistic framework to better understand the effects of CIIA in cellular reprogramming.