The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Ascorbic Acid Enhances Differentiation of Embryonic Stem Cells Into Cardiac Myocytes
Abstract
Background— Embryonic stem (ES) cells are capable of self-renewal and differentiation into cellular derivatives of all 3 germ layers. In appropriate culture conditions, ES cells can differentiate into specialized cells, including cardiac myocytes, but the efficiency is typically low and the process is incompletely understood. Methods and Results— We evaluated a chemical library for its potential to induce cardiac differentiation of ES cells in the absence of embryoid body formation. Using ES cells stably transfected with cardiac-specific α-cardiac myosin heavy chain (MHC) promoter-driven enhanced green fluorescent protein (EGFP), 880 compounds approved for human use were screened for their ability to induce cardiac differentiation. Treatment with ascorbic acid, also known as vitamin C, markedly increased the number of EGFP-positive cells, which displayed spontaneous and rhythmic contractile activity and stained positively for sarcomeric myosin and α-actinin. Furthermore, ascorbic acid induced the expression of cardiac genes, including GATA4, α-MHC, and β-MHC in untransfected ES cells in a developmentally controlled manner. This effect of ascorbic acid on cardiac differentiation was not mimicked by the other antioxidants such as N-acetylcysteine, Tiron, or vitamin E. Conclusions— Ascorbic acid induces cardiac differentiation in ES cells. This study demonstrates the potential for chemically modifying the cardiac differentiation program of ES cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Niwa, H., Miyazaki, J.-I., & Smith, A. G. (2000) · Nature Genetics · doi:10.1038/74199 · Cited by 3,596
Ascorbic acid: much more than just an antioxidant
Arrigoni, O., & De Tullio, M. C. (2002) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(01)00235-5 · Cited by 984
Differentiation of Pluripotent Embryonic Stem Cells Into Cardiomyocytes
Boheler, K. R., Czyz, J., Tweedie, D., Yang, H.-T., Anisimov, S. V., & Wobus, A. M. (2002) · Circulation Research · doi:10.1161/01.res.0000027865.61704.32 · Cited by 737
Isolation and characterization of the mouse cardiac myosin heavy chain genes
Gulick, J., Subramaniam, A., Neumann, J., & Robbins, J. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31568-0 · Cited by 330
Derivation and Potential Applications of Human Embryonic Stem Cells
Gepstein, L. (2002) · Circulation Research · doi:10.1161/01.res.0000041435.95082.84 · Cited by 247
Sauer, H., Rahimi, G., Hescheler, J., & Wartenberg, M. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01747-6 · Cited by 243
Embryonic stem cell differentiation: The role of extracellular factors
Czyz, J., & Wobus, A. M. (2001) · Differentiation · doi:10.1046/j.1432-0436.2001.680404.x · Cited by 240
Control of cardiac myosin heavy chain gene expression
Morkin, E. (2000) · Microscopy Research and Technique · doi:10.1002/1097-0029(20000915)50:6<522::aid-jemt9>3.0.co;2-u · Cited by 238
Hughes, S. (2002) · The Journal of Pathology · doi:10.1002/path.1159 · Cited by 89
Metzger, J. M., Lin, W.-I., Johnston, R. A., Westfall, M. V., & Samuelson, L. C. (1995) · Circulation Research · doi:10.1161/01.res.76.5.710 · Cited by 69
Cited by
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. (2005) · Nature Biotechnology · doi:10.1038/nbt1117 · Cited by 964
Increased Cardiomyocyte Differentiation from Human Embryonic Stem Cells in Serum‐Free Cultures
Passier, R., Oostwaard, D. W., Snapper, J., Kloots, J., Hassink, R. J., Kuijk, E., Roelen, B., de la Riviere, A. B., & Mummery, C. (2005) · STEM CELLS · doi:10.1634/stemcells.2004-0184 · Cited by 324
A role for chemistry in stem cell biology
Ding, S., & Schultz, P. G. (2004) · Nature Biotechnology · doi:10.1038/nbt987 · Cited by 311
Capturing Cardiogenesis in Gastruloids
Rossi, G., Broguiere, N., Miyamoto, M., Boni, A., Guiet, R., Girgin, M., Kelly, R. G., Kwon, C., & Lutolf, M. P. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2020.10.013 · Cited by 306
Metadata
- Authors
- Takahashi, T., Lord, B., Schulze, P. C., Fryer, R. M., Sarang, S. S., Gullans, S. R., & Lee, R. T.
- Venue
- Circulation
- Published
- 2003-04-15
- Volume
- 107
- Issue
- 14
- Pages
- 1912-1916
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2119288897
- Cited by
- 477
- References
- 12
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Ascorbic Acid Enhances Differentiation of Embryonic Stem Cells Into Cardiac Myocytes. https://app.cochat.ai/papers/10.1161/01.cir.0000064899.53876.a3
- The paper
- Takahashi, T., Lord, B., Schulze, P. C., Fryer, R. M., Sarang, S. S., Gullans, S. R., & Lee, R. T. (2003). Ascorbic Acid Enhances Differentiation of Embryonic Stem Cells Into Cardiac Myocytes. Circulation. https://doi.org/10.1161/01.cir.0000064899.53876.a3
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.