Article

A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog

Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Cell stem cell (Impact Factor: 22.27). 10/2009; 5(5):491-503. DOI: 10.1016/j.stem.2009.09.012
Source: PubMed

ABSTRACT

The combined activity of three transcription factors can reprogram adult cells into induced pluripotent stem cells (iPSCs). However, the transgenic methods used for delivering reprogramming factors have raised concerns regarding the future utility of the resulting stem cells. These uncertainties could be overcome if each transgenic factor were replaced with a small molecule that either directly activated its expression from the somatic genome or in some way compensated for its activity. To this end, we have used high-content chemical screening to identify small molecules that can replace Sox2 in reprogramming. We show that one of these molecules functions in reprogramming by inhibiting Tgf-beta signaling in a stable and trapped intermediate cell type that forms during the process. We find that this inhibition promotes the completion of reprogramming through induction of the transcription factor Nanog.

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Available from: Kyle M Loh, Jun 20, 2014
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    • "The sustained expression of somatic cell pathways and suppression of mesenchymal-to-epithelial transition (MET) are two major barriers in the initial stages of reprogramming (Li et al., 2010; Samavarchi-Tehrani et al., 2010). Suppression of the transforming growth factorb (TGF-b) pathway or activation of the bone morphogenetic protein (BMP) pathway promote MET and increase reprogramming efficiency (Ichida et al., 2009; Samavarchi- Tehrani et al., 2010). The class of partially reprogrammed cells that successfully pass through the initial stages and fail to activate the endogenous pluripotency genes are referred to as pre-iPSCs (Theunissen et al., 2011). "
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