The generation of induced pluripotent stem cells (iPSCs) achieved by 
overexpression of Oct4, Sox2, Klf4 and c-Myc, transformed our classical views of 
the cellular epigenetic landscape and delivered a new concept for cell and 
tissue engineering. In addition to iPSCs, several other cell types have also 
been generated by master transcription factor (TF)-mediated 
transdifferentiation. However, the critical molecular mechanisms amongst diverse 
cellular identity changes are not well understood. Through the investigation of 
reprogramming mechanisms, we recently revealed that over-expression of 
constitutive active Smad3 boosted not only iPSC generation, but also 3 other 
master TF-mediated conversions, from B cells to macrophages, myoblasts to 
adipocytes, and human fibroblasts to neurons. This demonstrated that there were 
common mechanisms underlying different master TF-mediated cell conversions. To 
illuminate such mechanisms further, we have recently performed 
CRISPR/Cas9-mediated genome-wide knockout screening during reprogramming with a 
lentiviral gRNA library containing 90,000 gRNAs. This screening provided us with 
~15 novel reprogramming roadblock genes as well as ~20 candidate genes essential 
for the reprogramming process but not for ES cell self-renewal. This data set 
will be a valuable resource to further understand how overexpression of master 
TFs alters cellular identity, and to achieve more faithful, efficient cell 
conversions for regenerative medicine.(Presented at the 1934th Meeting, March 
17, 2017).