Functional Genomics Reveals a BMP-Driven Mesenchymal-to-Epithelial Transition in the Initiation of Somatic Cell Reprogramming
Top Cited Papers
- 17 June 2010
- journal article
- research article
- Published by Elsevier BV in Cell Stem Cell
- Vol. 7 (1), 64-77
- https://doi.org/10.1016/j.stem.2010.04.015
Abstract
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. PaperClip /cms/asset/b7d91c75-1072-4889-a6bc-59bc8698d7ac/mmc5.mp3 Loading ... (mp3, 3.51 MB) Download audioKeywords
This publication has 38 references indexed in Scilit:
- Epithelial-Mesenchymal Transitions in Development and DiseaseCell, 2009
- A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing NanogCell Stem Cell, 2009
- Tgfβ Signal Inhibition Cooperates in the Induction of iPSCs and Replaces Sox2 and cMycCurrent Biology, 2009
- Nanog Is the Gateway to the Pluripotent Ground StateCell, 2009
- Role of the Murine Reprogramming Factors in the Induction of PluripotencyCell, 2009
- The Growth Factor Environment Defines Distinct Pluripotent Ground States in Novel Blastocyst-Derived Stem CellsCell, 2008
- A High-Efficiency System for the Generation and Study of Human Induced Pluripotent Stem CellsCell Stem Cell, 2008
- Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem CellsCell, 2008
- Sequential Expression of Pluripotency Markers during Direct Reprogramming of Mouse Somatic CellsCell Stem Cell, 2008
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006