The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
EZH2 and KDM6A Act as an Epigenetic Switch to Regulate Mesenchymal Stem Cell Lineage Specification
Open accessAbstract
The methyltransferase, Enhancer of Zeste homology 2 (EZH2), trimethylates histone 3 lysine 27 (H3K27me3) on chromatin and this repressive mark is removed by lysine demethylase 6A (KDM6A). Loss of these epigenetic modifiers results in developmental defects. We demonstrate that Ezh2 and Kdm6a transcript levels change during differentiation of multipotential human bone marrow-derived mesenchymal stem cells (MSC). Enforced expression of Ezh2 in MSC promoted adipogenic in vitro and inhibited osteogenic differentiation potential in vitro and in vivo, whereas Kdm6a inhibited adipogenesis in vitro and promoted osteogenic differentiation in vitro and in vivo. Inhibition of EZH2 activity and knockdown of Ezh2 gene expression in human MSC resulted in decreased adipogenesis and increased osteogenesis. Conversely, knockdown of Kdm6a gene expression in MSC leads to increased adipogenesis and decreased osteogenesis. Both Ezh2 and Kdm6a were shown to affect expression of master regulatory genes involved in adipogenesis and osteogenesis and H3K27me3 on the promoters of master regulatory genes. These findings demonstrate an important epigenetic switch centered on H3K27me3 which dictates MSC lineage determination. Stem Cells 2014;32:802–815
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
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052
Caplan, A. I. (1991) · Journal of Orthopaedic Research · doi:10.1002/jor.1100090504 · Cited by 6,548
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80258-5 · Cited by 4,244
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,529
Polycomb complexes repress developmental regulators in murine embryonic stem cells
Boyer, L. A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L. A., Lee, T. I., Levine, S. S., Wernig, M., Tajonar, A., Ray, M. K., et al. (2006) · Nature · doi:10.1038/nature04733 · Cited by 2,514
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
Agger, K., Cloos, P. A. C., Christensen, J., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A. E., & Helin, K. (2007) · Nature · doi:10.1038/nature06145 · Cited by 1,388
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,257
Gronthos, S., Zannettino, A. C. W., Hay, S. J., Shi, S., Graves, S. E., Kortesidis, A., & Simmons, P. J. (2003) · Journal of Cell Science · doi:10.1242/jcs.00369 · Cited by 1,024
Self-citationTAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation
Hong, J.-H., Hwang, E. S., McManus, M. T., Amsterdam, A., Tian, Y., Kalmukova, R., Mueller, E., Benjamin, T., Spiegelman, B. M., Sharp, P. A., et al. (2005) · Science · doi:10.1126/science.1110955 · Cited by 1,009
Adipogenesis: From Stem Cell to Adipocyte
Tang, Q. Q., & Lane, M. D. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052110-115718 · Cited by 902
Owen, M. (1988) · Journal of Cell Science · doi:10.1242/jcs.1988.supplement_10.5 · Cited by 830
Stabilization of Chromatin Structure by PRC1, a Polycomb Complex
Shao, Z., Raible, F., Mollaaghababa, R., Guyon, J. R., Wu, C.-T., Bender, W., & Kingston, R. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80604-2 · Cited by 822
A histone H3 lysine 27 demethylase regulates animal posterior development
Lan, F., Bayliss, P. E., Rinn, J. L., Whetstine, J. R., Wang, J. K., Chen, S., Iwase, S., Alpatov, R., Issaeva, I., Canaani, E., et al. (2007) · Nature · doi:10.1038/nature06192 · Cited by 783
The Polycomb Group Protein Suz12 Is Required for Embryonic Stem Cell Differentiation
Pasini, D., Bracken, A. P., Hansen, J. B., Capillo, M., & Helin, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01432-06 · Cited by 696
A Twist Code Determines the Onset of Osteoblast Differentiation
Bialek, P., Kern, B., Yang, X., Schrock, M., Sosic, D., Hong, N., Wu, H., Yu, K., Ornitz, D. M., Olson, E. N., et al. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00058-9 · Cited by 674
Caretti, G., Di Padova, M., Micales, B., Lyons, G. E., & Sartorelli, V. (2004) · Genes & Development · doi:10.1101/gad.1241904 · Cited by 600
Fouse, S. D., Shen, Y., Pellegrini, M., Cole, S., Meissner, A., Van Neste, L., Jaenisch, R., & Fan, G. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2007.12.011 · Cited by 452
Pereira, J. D., Sansom, S. N., Smith, J., Dobenecker, M.-W., Tarakhovsky, A., & Livesey, F. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002530107 · Cited by 451
Different Ezh2-Containing Complexes Target Methylation of Histone H1 or Nucleosomal Histone H3
Kuzmichev, A., Jenuwein, T., Tempst, P., & Reinberg, D. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00185-6 · Cited by 449
Wei, Y., Chen, Y.-H., Li, L.-Y., Lang, J., Yeh, S.-P., Shi, B., Yang, C.-C., Yang, J.-Y., Lin, C.-Y., Lai, C.-C., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2139 · Cited by 384
The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion
Kamminga, L. M., Bystrykh, L. V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., & de Haan, G. (2006) · Blood · doi:10.1182/blood-2005-09-3585 · Cited by 376
Kortesidis, A. (2005) · Blood · doi:10.1182/blood-2004-11-4349 · Cited by 363
Ezhkova, E., Lien, W.-H., Stokes, N., Pasolli, H. A., Silva, J. M., & Fuchs, E. (2011) · Genes & Development · doi:10.1101/gad.2019811 · Cited by 357
Siersbæk, R., Nielsen, R., John, S., Sung, M., Baek, S., Loft, A., Hager, G. L., & Mandrup, S. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.65 · Cited by 351
Histone Demethylases KDM4B and KDM6B Promotes Osteogenic Differentiation of Human MSCs
Ye, L., Fan, Z., Yu, B., Chang, J., Al Hezaimi, K., Zhou, X., Park, N.-H., & Wang, C.-Y. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.04.009 · Cited by 335
Signaling networks in RUNX2‐dependent bone development
Komori, T. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22994 · Cited by 329
Roles of Autocrine TGF-β Receptor and Smad Signaling in Adipocyte Differentiation
Choy, L., Skillington, J., & Derynck, R. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.3.667 · Cited by 321
UTX and UTY Demonstrate Histone Demethylase-Independent Function in Mouse Embryonic Development
Shpargel, K. B., Sengoku, T., Yokoyama, S., & Magnuson, T. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002964 · Cited by 308
Histone H3K27 methyltransferase Ezh2 represses Wnt genes to facilitate adipogenesis
Wang, L., Jin, Q., Lee, J.-E., Su, I.-H., & Ge, K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000031107 · Cited by 295
Lee, S., Lee, J. W., & Lee, S.-K. (2012) · Developmental Cell · doi:10.1016/j.devcel.2011.11.009 · Cited by 252
Fujiki, K., Kano, F., Shiota, K., & Murata, M. (2009) · BMC Biology · doi:10.1186/1741-7007-7-38 · Cited by 242
Zhou, S., Eid, K., & Glowacki, J. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301239 · Cited by 226
Stromal Mechanisms of Bone Marrow: Cloning in Vitro and Retransplantation in Vivo
Friedenstein, A. J. (1980) · Haematology and Blood Transfusion / Hämatologie und Bluttransfusion · doi:10.1007/978-3-642-67319-1_3 · Cited by 225
Isenmann, S., Arthur, A., Zannettino, A. C., Turner, J. L., Shi, S., Glackin, C. A., & Gronthos, S. (2009) · Stem Cells · doi:10.1002/stem.181 · Cited by 210
Self-citationReciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation
Ichida, F., Nishimura, R., Hata, K., Matsubara, T., Ikeda, F., Hisada, K., Yatani, H., Cao, X., Komori, T., Yamaguchi, A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403621200 · Cited by 173
Recruitment of Drosophila Polycomb group proteins to chromatin by DSP1
Déjardin, J., Rappailles, A., Cuvier, O., Grimaud, C., Decoville, M., Locker, D., & Cavalli, G. (2005) · Nature · doi:10.1038/nature03386 · Cited by 157
Modifications of RNA polymerase II are pivotal in regulating gene expression states
Brookes, E., & Pombo, A. (2009) · EMBO Reports · doi:10.1038/embor.2009.221 · Cited by 154
The histone demethylase UTX enables RB-dependent cell fate controlPreprint
Wang, J. K., Tsai, M.-C., Poulin, G. B., Adler, A. S., Chen, S., Liu, H., Shi, Y., & Chang, H. Y. (2010) · Genes & Development · doi:10.1101/gad.1882610 · Cited by 151
Cakouros, D., Isenmann, S., Cooper, L., Zannettino, A. C. W., Anderson, P. J., Glackin, C. A., & Gronthos, S. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06315-11 · Cited by 124
Self-citationThe H3K27me3 Demethylase dUTX Is a Suppressor of Notch- and Rb-Dependent Tumors in Drosophila
Herz, H., Madden, L. D., Chen, Z., Bolduc, C., Buff, E. M., Gupta, R., Davuluri, R. V., Shilatifard, A., Hariharan, I. K., & Bergmann, A. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01633-09 · Cited by 116
Noer, A., Boquest, A. C., & Collas, P. (2007) · BMC Cell Biology · doi:10.1186/1471-2121-8-18 · Cited by 112
Noer, A., Lindeman, L. C., & Collas, P. (2008) · Stem Cells and Development · doi:10.1089/scd.2008.0189 · Cited by 97
Menicanin, D., Bartold, P. M., Zannettino, A. C. W., & Gronthos, S. (2010) · Stem Cells and Development · doi:10.1089/scd.2009.0492 · Cited by 86
Self-citationGlazer, R. I., Knode, M. C., Tseng, C. K. H., et al. (1986) · Biochemical Pharmacology · doi:10.1016/0006-2952(86)90774-4 · Cited by 77
Kuznetsov, S. A., Mankani, M. H., Leet, A. I., Ziran, N. M., Gronthos, S., & Robey, P. G. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0140 · Cited by 72
Self-citationFitter, S., Vandyke, K., Gronthos, S., & Zannettino, A. C. W. (2012) · Journal of Molecular Endocrinology · doi:10.1530/jme-12-0003 · Cited by 68
Self-citationEpigenetic Control of Hematopoietic Stem Cell Aging The Case of Ezh2
de Haan, G., & GERRITS, A. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1392.008 · Cited by 42
Cited by
Programmed cell senescence in skeleton during late puberty
Li, C., Chai, Y., Wang, L., Gao, B., Chen, H., Gao, P., Zhou, F.-Q., Luo, X., Crane, J. L., Yu, B., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01509-0 · Cited by 92
Allegra, A., Casciaro, M., Barone, P., Musolino, C., & Gangemi, S. (2022) · Cancers · doi:10.3390/cancers14112597 · Cited by 19
Metadata
- Authors
- Hemming, S., Cakouros, D., Isenmann, S., Cooper, L., Menicanin, D., Zannettino, A., & Gronthos, S.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-02-19
- Volume
- 32
- Issue
- 3
- Pages
- 802-815
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W1553969934
- Cited by
- 259
- References
- 49
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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
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.
