Cell Stem Cell. 2010 Jul 2;7(1):64-77. doi: 10.1016/j.stem.2010.04.015. Epub 2010 Jun 17.

Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming.

Samavarchi-Tehrani P, Golipour A, David L, Sung HK, Beyer TA, Datti A, Woltjen K, Nagy A, Wrana JL.

Source

Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

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:

Comment in

When fibroblasts MET iPSCs. [Cell Stem Cell. 2010]
When fibroblasts MET iPSCs.Polo JM, Hochedlinger K. Cell Stem Cell. 2010 Jul 2; 7(1):5-6. Epub 2010 Jun 17.

PMID:: 20621051; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Secondary Source ID, Grant Support

Publication Types

Research Support, Non-U.S. Gov't

MeSH Terms

Substances

Secondary Source ID

GEO/GSE21757

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Supplemental Content

Save items

Related citations in PubMed

A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. [Cell Stem Cell. 2010]
A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.
Li R, Liang J, Ni S, Zhou T, Qing X, Li H, He W, Chen J, Li F, Zhuang Q, et al. Cell Stem Cell. 2010 Jul 2; 7(1):51-63. Epub 2010 Jun 17.
Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells. [Biomaterials. 2011]
Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells.
Li HY, Chien Y, Chen YJ, Chen SF, Chang YL, Chiang CH, Jeng SY, Chang CM, Wang ML, Chen LK, et al. Biomaterials. 2011 Sep; 32(26):5994-6005. Epub 2011 Jun 11.
Optimal reprogramming factor stoichiometry increases colony numbers and affects molecular characteristics of murine induced pluripotent stem cells. [Cytometry A. 2011]
Optimal reprogramming factor stoichiometry increases colony numbers and affects molecular characteristics of murine induced pluripotent stem cells.
Tiemann U, Sgodda M, Warlich E, Ballmaier M, Schöler HR, Schambach A, Cantz T. Cytometry A. 2011 Jun; 79(6):426-35. Epub 2011 May 4.
Review Direct reprogramming 101. [Dev Growth Differ. 2010]
Review Direct reprogramming 101.
Takahashi K. Dev Growth Differ. 2010 Apr; 52(3):319-33. Epub 2010 Mar 7.
Review The genetics of induced pluripotency. [Reproduction. 2010]
Review The genetics of induced pluripotency.
Ralston A, Rossant J. Reproduction. 2010 Jan; 139(1):35-44.

See reviews... See all...

Cited by 63 PubMed Central articles

No factor left behind: generation of transgene-free induced pluripotent stem cells. [Am J Stem Cells. 2012]
No factor left behind: generation of transgene-free induced pluripotent stem cells.
Li M, Izpisua Belmonte JC. Am J Stem Cells. 2012; 1(1):75-80. Epub 2011 Sep 19.
Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles. [Proc Natl Acad Sci U S A. 2013]
Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles.
Hikichi T, Matoba R, Ikeda T, Watanabe A, Yamamoto T, Yoshitake S, Tamura-Nakano M, Kimura T, Kamon M, Shimura M, et al. Proc Natl Acad Sci U S A. 2013 Apr 16; 110(16):6412-7. Epub 2013 Apr 2.
Cell reprogramming requires silencing of a core subset of polycomb targets. [PLoS Genet. 2013]
Cell reprogramming requires silencing of a core subset of polycomb targets.
Fragola G, Germain PL, Laise P, Cuomo A, Blasimme A, Gross F, Signaroldi E, Bucci G, Sommer C, Pruneri G, et al. PLoS Genet. 2013 Feb; 9(2):e1003292. Epub 2013 Feb 28.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
GEO DataSets
Gene expression and molecular abundance data reported in the current articles that are also included in the curated Gene Expression Omnibus (GEO) DataSets.
Related Project
Related Projects
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in...
Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming.
Cell Stem Cell. 2010 Jul 2 ;7(1):64-77. doi: 10.1016/j.stem.2010.04.015. Epub 2010 Jun 17 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: