A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog
Open accessAbstract
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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E-616452 (RepSox) is a TGF-β inhibitor that has been used to replace SOX2 during epigenetic reprogramming.
“E-616452, also known as RepSox, is a TGF-β inhibitor that has been used in experiments to replace SOX2 during epigenetic reprogramming [68, 69].”
From Chemically induced reprogramming to reverse cellular aging (2023) · cites this paper as [68]
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- Authors
- Ichida, J. K., Blanchard, J., Lam, K., Son, E. Y., Chung, J. E., Egli, D., Loh, K. M., Carter, A. C., Di Giorgio, F. P., Koszka, K., Huangfu, D., Akutsu, H., Liu, D. R., Rubin, L. L., & Eggan, K.
- Affiliations
- Stowers Institute for Medical Research (US)
- Harvard University (US)
- National Research Institute for Child Health and Development (JP)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rubin, Lee L.
- Eggan, Kevin
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 5
- Issue
- 5
- Pages
- 491-503
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3335195
- OpenAlex
- W2151220680
- Cited by
- 808
- References
- 39
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 21 · 2023: 29 · 2022: 21 · 2021: 34 · 2020: 29 · 2019: 35 · 2018: 45 · 2017: 36 · 2016: 46 · 2015: 64 · 2014: 80 · 2013: 84 · 2012: 89
- FWCI
- 33.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (GM 065400, R01GM065400)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046732)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- induced pluripotent stem cells, cellular reprogramming, small molecule inhibitors, TGF-beta signaling, SOX2, Nanog, transcription factors, compound screening, somatic cell reprogramming
- MeSH terms
- Nanog Homeobox Protein, Animals, Antibodies, Monoclonal, Benzamides, Cell Line, Dioxoles, Pyrazoles, Pyridines, Transduction, Genetic, Signal Transduction, Transforming Growth Factor beta, Receptors, Transforming Growth Factor beta, Homeodomain Proteins, Mice, Cell Transdifferentiation, Small Molecule Libraries, SOXB1 Transcription Factors, Induced Pluripotent Stem Cells, High-Throughput Screening Assays
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