TY - JOUR
T1 - Functional genomics reveals a BMP-Driven mesenchymal-to-Epithelial transition in the initiation of somatic cell reprogramming
AU - Samavarchi-Tehrani, Payman
AU - Golipour, Azadeh
AU - David, Laurent
AU - Sung, Hoon Ki
AU - Beyer, Tobias A.
AU - Datti, Alessandro
AU - Woltjen, Knut
AU - Nagy, Andras
AU - Wrana, Jeffrey L.
PY - 2010
Y1 - 2010
N2 - Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by expression of defined embryonic factors. However, little is known of the molecular mechanisms underlying the reprogramming process. Here we explore somatic cell reprogramming by exploiting a secondary mouse embryonic fibroblast model that forms iPSCs with high efficiency upon inducible expression of Oct4, Klf4, c-Myc, and Sox2. Temporal analysis of gene expression revealed that reprogramming is a multistep process that is characterized by initiation, maturation, and stabilization phases. Functional analysis by systematic RNAi screening further uncovered a key role for BMP signaling and the induction of mesenchymal-to-epithelial transition (MET) during the initiation phase. We show that this is linked to BMP-dependent induction of miR-205 and the miR-200 family of microRNAs that are key regulators of MET. These studies thus define a multistep mechanism that incorporates a BMP-miRNA-MET axis during somatic cell reprogramming.
AB - Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by expression of defined embryonic factors. However, little is known of the molecular mechanisms underlying the reprogramming process. Here we explore somatic cell reprogramming by exploiting a secondary mouse embryonic fibroblast model that forms iPSCs with high efficiency upon inducible expression of Oct4, Klf4, c-Myc, and Sox2. Temporal analysis of gene expression revealed that reprogramming is a multistep process that is characterized by initiation, maturation, and stabilization phases. Functional analysis by systematic RNAi screening further uncovered a key role for BMP signaling and the induction of mesenchymal-to-epithelial transition (MET) during the initiation phase. We show that this is linked to BMP-dependent induction of miR-205 and the miR-200 family of microRNAs that are key regulators of MET. These studies thus define a multistep mechanism that incorporates a BMP-miRNA-MET axis during somatic cell reprogramming.
UR - http://www.scopus.com/inward/record.url?scp=77956320116&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2010.04.015
DO - 10.1016/j.stem.2010.04.015
M3 - Article
C2 - 20621051
AN - SCOPUS:77956320116
SN - 1934-5909
VL - 7
SP - 64
EP - 77
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -