The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Endogenous Wnt/β-Catenin Signaling Is Required for Cardiac Differentiation in Human Embryonic Stem Cells
Open accessAbstract
BACKGROUND: Wnt/beta-catenin signaling is an important regulator of differentiation and morphogenesis that can also control stem cell fates. Our group has developed an efficient protocol to generate cardiomyocytes from human embryonic stem (ES) cells via induction with activin A and BMP4. METHODOLOGY/PRINCIPAL FINDINGS: We tested the hypothesis that Wnt/beta-catenin signals control both early mesoderm induction and later cardiac differentiation in this system. Addition of exogenous Wnt3a at the time of induction enhanced cardiac differentiation, while early inhibition of endogenous Wnt/beta-catenin signaling with Dkk1 inhibited cardiac differentiation, as indicated by quantitative RT-PCR analysis for beta-myosin heavy chain (beta-MHC), cardiac troponin T (cTnT), Nkx2.5, and flow cytometry analysis for sarcomeric myosin heavy chain (sMHC). Conversely, late antagonism of endogenously produced Wnts enhanced cardiogenesis, indicating a biphasic role for the pathway in human cardiac differentiation. Using quantitative RT-PCR, we show that canonical Wnt ligand expression is induced by activin A/BMP4 treatment, and the extent of early Wnt ligand expression can predict the subsequent efficiency of cardiogenesis. Measurement of Brachyury expression showed that addition of Wnt3a enhances mesoderm induction, whereas blockade of endogenously produced Wnts markedly inhibits mesoderm formation. Finally, we show that Wnt/beta-catenin signaling is required for Smad1 activation by BMP4. CONCLUSIONS/SIGNIFICANCE: Our data indicate that induction of mesoderm and subsequent cardiac differentiation from human ES cells requires fine-tuned cross talk between activin A/BMP4 and Wnt/beta-catenin pathways. Controlling these pathways permits efficient generation of cardiomyocytes for basic studies or cardiac repair applications.
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Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1327 · Cited by 2,206
Self-citationFeeder-free growth of undifferentiated human embryonic stem cells
Xu, C., Inokuma, M. S., Denham, J., Golds, K., Kundu, P., Gold, J. D., & Carpenter, M. K. (2001) · Nature Biotechnology · doi:10.1038/nbt1001-971 · Cited by 1,870
Kehat, I., Kenyagin‐Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz‐Eldor, J., & Gepstein, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12131 · Cited by 1,814
Murry, C. E., & Keller, G. (2008) · Cell · doi:10.1016/j.cell.2008.02.008 · Cited by 1,729
Self-citationCharacterization and Enrichment of Cardiomyocytes Derived From Human Embryonic Stem Cells
Xu, C., Police, S., Rao, N., & Carpenter, M. K. (2002) · Circulation Research · doi:10.1161/01.res.0000035254.80718.91 · Cited by 902
Ueno, S., Weidinger, G., Osugi, T., Kohn, A. D., Golob, J. L., Pabon, L., Reinecke, H., Moon, R. T., & Murry, C. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702859104 · Cited by 613
Self-citationInhibition of Wnt activity induces heart formation from posterior mesoderm
Marvin, M. J., Di Rocco, G., Gardiner, A., Bush, S. M., & Lassar, A. B. (2001) · Genes & Development · doi:10.1101/gad.855501 · Cited by 590
Gadue, P., Huber, T. L., Paddison, P. J., & Keller, G. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603916103 · Cited by 560
Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal
Fuentealba, L. C., Eivers, E., Ikeda, A., Hurtado, C., Kuroda, H., Pera, E. M., & De Robertis, E. M. (2007) · Cell · doi:10.1016/j.cell.2007.09.027 · Cited by 554
Wnt antagonism initiates cardiogenesis in Xenopus laevis
Schneider, V. A., & Mercola, M. (2001) · Genes & Development · doi:10.1101/gad.855601 · Cited by 483
Cited by
Lian, X., Hsiao, C., Wilson, G., Zhu, K., Hazeltine, L. B., Azarin, S. M., Raval, K. K., Zhang, J., Kamp, T. J., & Palecek, S. P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200250109 · Cited by 1,717
Lian, X., Zhang, J., Azarin, S. M., Zhu, K., Hazeltine, L. B., Bao, X., Hsiao, C., Kamp, T. J., & Palecek, S. P. (2013) · Nature Protocols · doi:10.1038/nprot.2012.150 · Cited by 1,748
Chemically defined generation of human cardiomyocytes
Burridge, P. W., Matsa, E., Shukla, P., Lin, Z. C., Churko, J. M., Ebert, A. D., Lan, F., Diecke, S., Huber, B., Mordwinkin, N. M., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2999 · Cited by 1,606
Laflamme, M. A., & Murry, C. E. (2011) · Nature · doi:10.1038/nature10147 · Cited by 1,206
Self-citationKattman, S. J., Witty, A. D., Gagliardi, M., Dubois, N. C., Niapour, M., Hotta, A., Ellis, J., & Keller, G. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2010.12.008 · Cited by 1,159
Metadata
- Authors
- Paige, S. L., Osugi, T., Afanasiev, O. K., Pabon, L., Reinecke, H., & Murry, C. E.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-06-15
- Volume
- 5
- Issue
- 6
- Pages
- e11134
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2062611303
- Cited by
- 273
- References
- 22
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- gold
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