Dnmt3a is essential for hematopoietic stem cell differentiation
Open accessAbstract
Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem cells obstructs differentiation; however, the role of these enzymes in somatic stem cells is largely unknown. Using conditional ablation, we show that Dnmt3a loss progressively impairs hematopoietic stem cell (HSC) differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow. Dnmt3a-null HSCs show both increased and decreased methylation at distinct loci, including substantial CpG island hypermethylation. Dnmt3a-null HSCs upregulate HSC multipotency genes and downregulate differentiation factors, and their progeny exhibit global hypomethylation and incomplete repression of HSC-specific genes. These data establish Dnmt3a as a critical participant in the epigenetic silencing of HSC regulatory genes, thereby enabling efficient differentiation.
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DNMT3A loss-of-function does not lead to global DNA methylation changes.
“This reinforces previous findings that DNMT3A loss-of-function does not lead to global DNA methylation changes (15,16,19)”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [15]
The Results section reports no overall difference in whole-genome 5-methylcytosine levels between transplanted control and Dnmt3a-null hematopoietic stem cells. This supports the claim for those cells, but not an unqualified statement about DNMT3A loss-of-function in other cell types. The same section also reports methylation changes at specific genomic regions. (LLM, conf=0.82)
Experimental — accuracy not yet measuredDnmt3a−/− HSCs demonstrate defective differentiation and enhanced self-renewal.
“prior studies showed that Dnmt3a−/− HSCs demonstrate defective differentiation and enhanced self-renewal (Challen et al., 2011; Jeong et al., 2018)”
From Chronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling (2021) · cites this paper as Challen et al., 2011
Mouse models show Dnmt3a loss-of-function skews hematopoietic stem cell fate decisions toward self-renewal, facilitating clonal expansion in the bone marrow.
“Mouse models show Dnmt3a loss-of-function skews HSC fate decisions toward self-renewal, facilitating clonal expansion in the bone marrow (BM; ref. 15,16).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [15]
Analysis of DNA methylation and gene expression patterns in mouse and human systems has yet to identify a unifying molecular mechanism to explain the increased fitness of Dnmt3a-mutant hematopoietic stem cells.
“However, analysis of DNA methylation and gene expression patterns in mouse (15,17) and human (17,18) systems have yet to identify a unifying molecular mechanism to explain the increased fitness of these mutant HSCs.”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [15]
Genetic deletion of IFNgr1 in Dnmt3a KO hematopoietic stem cells normalized gene expression, including the previously reported upregulation of hematopoietic stem cell stemness genes.
“In support of the functional data, genetic deletion of IFNgr1 in Dnmt3a KO HSCs normalized gene expression, including the previously reported (15) upregulation of HSC “stemness” genes (Supplementary Fig. S5A).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [15]
TET2-mutant myeloid cells exhibit altered cytokine production, notably IL-1β, and inflammatory signaling, which has been directly linked to increased cardiovascular risk.
“TET2-mutant myeloid cells exhibit altered cytokine production (notably IL-1ß) and inflammatory signaling, which has been directly linked to increased cardiovascular risk [6,31].”
From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [31]
The Results section on multipotency gene upregulation examines Dnmt3a-null hematopoietic stem cells and their differentiation-related gene expression. Searches for TET2-mutant myeloid cells, IL-1β, inflammatory signaling, and cardiovascular risk found no passage in our copy addressing the attributed claim. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIn unmanipulated mice, there were few significantly differentially expressed genes between control and Dnmt3a KO hematopoietic stem cells.
“In unmanipulated mice, there were few significantly differentially expressed genes (DEG) between control and Dnmt3a KO HSCs (Fig. 4A), consistent with prior studies (15).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [15]
The Results section on multipotency gene upregulation reports 516 differentially expressed genes between transplanted Dnmt3a-null and control HSCs. The Microarrays methods specify that the profiled HSCs came from secondary recipient mice. Our copy does not report the number of differentially expressed genes between these groups in unmanipulated mice, so it cannot verify the cited comparison. (LLM, conf=0.78)
Experimental — accuracy not yet measuredLoss of DNMT3a impairs hematopoietic stem cell differentiation while increasing their number in the bone marrow.
“In this regard, loss of DNMT3a impairs differentiation of HSCs while their number increases in the bone marrow (91)”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [91]
Haematopoietic stem cells from mice with conditional deletion of these genes show an increased self-renewal capacity, allowing them to outcompete non-mutated HSC and clonally expand.
“Haematopoietic stem cells (HSC) from these mice show an increased self-renewal capacity, allowing them to outcompete non-mutated HSC and clonally expand 80-85 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [85]
Mouse models carrying loss-of-function mutations in either TET2 or DNMT3A show an HSC competitive advantage in vivo as well as a propensity for leukemia when cooperating mutations are present.
“Mouse models carrying loss-of-function mutations in either of these genes clearly show an HSC competitive advantage in vivo as well as a propensity for leukemia when cooperating mutations are present 50–53.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [51]
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Cites
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143 · see citing works
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836 · see citing works
Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673 · see citing works
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Goodell, M. A., Brose, K., Paradis, G. A., Conner, A. N., & Mulligan, R. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1797 · Cited by 2,902 · see citing works
Self-citationGenome-scale DNA methylation maps of pluripotent and differentiated cells
Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B., et al. (2008) · Nature · doi:10.1038/nature07107 · Cited by 2,536 · see citing works
Self-citationLinking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · see citing works
<i>DNMT3A</i> Mutations in Acute Myeloid Leukemia
Ley, T. J., Ding, L., Walter, M. J., McLellan, M. D., Lamprecht, T., Larson, D. E., Kandoth, C., Payton, J. E., Baty, J., Welch, J., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1005143 · Cited by 1,983 · see citing works
Okuda, T., van Deursen, J., Hiebert, S. W., Grosveld, G., & Downing, J. R. (1996) · Cell · doi:10.1016/s0092-8674(00)80986-1 · Cited by 1,856 · see citing works
Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases
Okano, M., Xie, S., & Li, E. (1998) · Nature Genetics · doi:10.1038/890 · Cited by 1,643 · see citing works
Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages
Scott, E. W., Simon, M. C., Anastasi, J., & Singh, H. (1994) · Science · doi:10.1126/science.8079170 · Cited by 1,532 · see citing works
Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting
Kaneda, M., Okano, M., Hata, K., Sado, T., Tsujimoto, N., Li, E., & Sasaki, H. (2004) · Nature · doi:10.1038/nature02633 · Cited by 1,392 · see citing works
Hematopoietic Stem Cell Quiescence Maintained by p21 <sup>cip1/waf1</sup>
Cheng, T., Rodrigues, N., Shen, H., Yang, Y.-G., Dombkowski, D., Sykes, M., & Scadden, D. T. (2000) · Science · doi:10.1126/science.287.5459.1804 · Cited by 1,339 · see citing works
BSMAP: whole genome bisulfite sequence MAPping program
Xi, Y., & Li, W. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-232 · Cited by 1,216 · see citing works
Self-citationThe ikaros gene is required for the development of all lymphoid lineages
Georgopoulos, K., Bigby, M., Wang, J.-H., Molnar, A., Wu, P., Winandy, S., & Sharpe, A. (1994) · Cell · doi:10.1016/0092-8674(94)90407-3 · Cited by 985 · see citing works
Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C., & Goodell, M. A. (2010) · Nature · doi:10.1038/nature09135 · Cited by 877 · see citing works
Self-citationDe novo DNA cytosine methyltransferase activities in mouse embryonic stem cells
Lei, H., Oh, S. P., Okano, M., Jüttermann, R., Goss, K. A., Jaenisch, R., & Li, E. (1996) · Development · doi:10.1242/dev.122.10.3195 · Cited by 816 · see citing works
Yan, X., Xu, J., Gu, Z., Pan, C., Lü, G., Shen, Y., Shi, J., Zhu, Y., Tang, L., Zhang, X., et al. (2011) · Nature Genetics · doi:10.1038/ng.788 · Cited by 806 · see citing works
Chen, T., Ueda, Y., Dodge, J. E., Wang, Z., & Li, E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5594-5605.2003 · Cited by 751 · see citing works
Wilson, N. K., Foster, S. D., Wang, X., Knezevic, K., Schütte, J., Kaimakis, P., Chilarska, P. M., Kinston, S., Ouwehand, W. H., Dzierzak, E., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.07.016 · Cited by 728 · see citing works
Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
Wu, H., Coskun, V., Tao, J., Xie, W., Ge, W., Yoshikawa, K., Li, E., Zhang, Y., & Sun, Y. E. (2010) · Science · doi:10.1126/science.1190485 · Cited by 604 · see citing works
DNA methyltransferases control telomere length and telomere recombination in mammalian cells
Gonzalo, S., Jaco, I., Fraga, M. F., Chen, T., Li, E., Esteller, M., & Blasco, M. A. (2006) · Nature Cell Biology · doi:10.1038/ncb1386 · Cited by 604 · see citing works
Distinct Hematopoietic Stem Cell Subtypes Are Differentially Regulated by TGF-β1
Challen, G. A., Boles, N. C., Chambers, S. M., & Goodell, M. A. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.02.002 · Cited by 580 · see citing works
Self-citationMackarehtschian, K., Hardin, J. D., Moore, K., Boast, S., Goff, S. P., & Lemischka, I. R. (1995) · Immunity · doi:10.1016/1074-7613(95)90167-1 · Cited by 575 · see citing works
Recurrent DNMT3A mutations in patients with myelodysplastic syndromes
Walter, M. J., Ding, L., Shen, D., Shao, J., Grillot, M., McLellan, M., Fulton, R., Schmidt, H., Kalicki-Veizer, J., O'Laughlin, M., et al. (2011) · Leukemia · doi:10.1038/leu.2011.44 · Cited by 527 · see citing works
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction
Bröske, A.-M., Vockentanz, L., Kharazi, S., Huska, M. R., Mancini, E., Scheller, M., Kuhl, C., Enns, A., Prinz, M., Jaenisch, R., et al. (2009) · Nature Genetics · doi:10.1038/ng.463 · Cited by 478 · see citing works
DNA methylation and the regulation of gene transcription
Attwood, J. T., Yung, R. L., & Richardson, B. C. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8420-z · Cited by 426 · see citing works
Trowbridge, J. J., Snow, J. W., Kim, J., & Orkin, S. H. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.08.016 · Cited by 373 · see citing works
Molecular Signatures of Proliferation and Quiescence in Hematopoietic Stem Cells
Bowman, T. V., Merchant, A. A., Ramos, C. A., Whitehouse, N. L., Young, A., Shaw, C. A., & Goodell, M. A. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020301 · Cited by 363 · see citing works
Self-citationDependence of histone modifications and gene expression on DNA hypermethylation in cancer.
Fahrner, J. A., Eguchi, S., Herman, J. G., & Baylin, S. B. (2002) · PubMed · Cited by 355 · see citing works
Mouse hematopoietic stem cell identification and analysis
Challen, G. A., Boles, N. C., Lin, K. K., & Goodell, M. A. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20674 · Cited by 350 · see citing works
Self-citationAllsopp, R. C., Morin, G. B., DePinho, R., Harley, C. B., & Weissman, I. L. (2003) · Blood · doi:10.1182/blood-2002-07-2334 · Cited by 324 · see citing works
Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution
Gu, H., Bock, C., Mikkelsen, T. S., Jäger, N., Smith, Z. D., Tomazou, E. M., Gnirke, A., Lander, E. S., & Meissner, A. (2010) · Nature Methods · doi:10.1038/nmeth.1414 · Cited by 324 · see citing works
Self-citationHematopoietic Fingerprints: An Expression Database of Stem Cells and Their Progeny
Chambers, S. M., Boles, N. C., Lin, K. K., Tierney, M., Bowman, T. V., Bradfute, S. B., Chen, A. J., Merchant, A. A., Sirin, O., Weksberg, D. C., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.10.003 · Cited by 318 · see citing works
Self-citationA rapid micro chromatin immunoprecipitation assay (ChIP)
Dahl, J. A., & Collas, P. (2008) · Nature Protocols · doi:10.1038/nprot.2008.68 · Cited by 284 · see citing works
Array-based genomic resequencing of human leukemia
Yamashita, Y., Yuan, J., Suetake, I., Suzuki, H., Ishikawa, Y., Choi, Y. L., Ueno, T., Soda, M., Hamada, T., Haruta, H., et al. (2010) · Oncogene · doi:10.1038/onc.2010.117 · Cited by 250 · see citing works
Song, L., James, S. R., Kazim, L., & Karpf, A. R. (2004) · Analytical Chemistry · doi:10.1021/ac0489420 · Cited by 242 · see citing works
Pbx1 Regulates Self-Renewal of Long-Term Hematopoietic Stem Cells by Maintaining Their Quiescence
Ficara, F., Murphy, M., Lin, M., & Cleary, M. L. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.03.004 · Cited by 235 · see citing works
High-throughput bisulfite sequencing in mammalian genomes
Smith, Z. D., Gu, H., Bock, C., Gnirke, A., & Meissner, A. (2009) · Methods · doi:10.1016/j.ymeth.2009.05.003 · Cited by 216 · see citing works
Self-citationTadokoro, Y., Ema, H., Okano, M., Li, E., & Nakauchi, H. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20060750 · Cited by 203 · see citing works
Hypomethylation and hypermethylation of DNA in Wilms tumors
Ehrlich, M., Jiang, G., Fiala, E. S., Dome, J. S., Yu, M. C., Long, T. I., Youn, B., Sohn, O. S., Widschwendter, M., Tomlinson, G. E., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205890 · Cited by 174 · see citing works
Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse
Kroeger, H., Jelı́nek, J., Estecio, M. R., He, R. L., Kondo, K., Chung, W., Zhang, L., Shen, L., Kantarjian, H. M., Bueso-Ramos, C., et al. (2008) · Blood · doi:10.1182/blood-2007-11-126227 · Cited by 159 · see citing works
Self-citationDifferential DNA hypermethylation and hypomethylation signatures in colorectal cancer
Frigola, J., Solé, X., Paz, M. F., Moreno, V. R., Esteller, M., Capellá, G., & Peinado, M. A. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi028 · Cited by 152 · see citing works
Regulation of Lymphoid versus Myeloid Fate 'choice' by the Transcription Factor Mef2c
Stehling-Sun, S., Dade, J., Nutt, S. L., DeKoter, R. P., & Camargo, F. D. (2009) · Nature Immunology · doi:10.1038/ni.1694 · Cited by 125 · see citing works
Cho, Y. H., Yazıcı, H., Wu, H., Terry, M. B., González, K., Qu, M., Dalay, N., & Santella, R. M. (2010) · PubMed · Cited by 125 · see citing works
The p47 GTPase Lrg-47 (Irgm1) Links Host Defense and Hematopoietic Stem Cell Proliferation
Feng, C. G., Weksberg, D. C., Taylor, G. A., Sher, A., & Goodell, M. A. (2008) · Cell stem cell · doi:10.1016/j.stem.2007.10.007 · Cited by 124 · see citing works
Self-citationChallen, G. A., & Goodell, M. A. (2010) · Experimental Hematology · doi:10.1016/j.exphem.2010.02.011 · Cited by 103 · see citing works
Self-citationThe orphan nuclear receptor Nurr1 restricts the proliferation of haematopoietic stem cells
Sirin, O., Lukov, G. L., Mao, R., Conneely, O. M., & Goodell, M. A. (2010) · Nature Cell Biology · doi:10.1038/ncb2125 · Cited by 96 · see citing works
Self-citationEnforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis
Chen, D., & Zhang, G. (2001) · Experimental Hematology · doi:10.1016/s0301-472x(01)00670-1 · Cited by 68 · see citing works
Jelı́nek, J., Liang, S., Estecio, M. R., et al. (2009) · Blood · doi:10.1182/blood.v114.22.567.567 · Cited by 2 · see citing works
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Flagged first, then by citations
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Sorted by citations
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061 · see citing works
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841 · see citing works
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531 · see citing works
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045 · see citing works
Self-citationClonal hematopoiesis and risk of atherosclerotic cardiovascular disease
Jaiswal, S., Natarajan, P., Silver, A. J., Gibson, C. J., Bick, A. G., Shvartz, E., McConkey, M., Gupta, N., Gabriel, S., Ardissino, D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701719 · Cited by 2,683 · see citing works
Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia
Shlush, L. I., Zandi, S., Mitchell, A., Chen, W. C., Brandwein, J. M., Gupta, V., Kennedy, J. A., Schimmer, A. D., Schuh, A. C., Yee, K. W., et al. (2014) · Nature · doi:10.1038/nature13038 · Cited by 1,443 · see citing works
Clonal hematopoiesis in human aging and disease
Jaiswal, S., & Ebert, B. L. (2019) · Science · doi:10.1126/science.aan4673 · Cited by 1,156 · see citing works
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793 · see citing works
Sun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.03.002 · Cited by 686 · see citing works
Self-citationClonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults
Young, A. L., Challen, G. A., Birmann, B. M., & Druley, T. E. (2016) · Nature Communications · doi:10.1038/ncomms12484 · Cited by 692 · see citing works
Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia
Yoshizato, T., Dumitriu, B., Hosokawa, K., Makishima, H., Yoshida, K., Townsley, D., Sato-Otsubo, A., Sato, Y., Liu, D., Suzuki, H., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414799 · Cited by 646 · see citing works
The ageing haematopoietic stem cell compartment
Geiger, H., de Haan, G., & Florian, M. C. (2013) · Nature Reviews Immunology · doi:10.1038/nri3433 · Cited by 604 · see citing works
The roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549 · see citing works
Heckl, D., Kowalczyk, M. S., Yudovich, D., Belizaire, R., Puram, R. V., McConkey, M. E., Thielke, A., Aster, J. C., Regev, A., & Ebert, B. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2951 · Cited by 555 · see citing works
The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape
Weinberg, D. N., Papillon-Cavanagh, S., Chen, H., Yue, Y., Chen, X., Rajagopalan, K. N., Horth, C., McGuire, J. T., Xu, X., Nikbakht, H., et al. (2019) · Nature · doi:10.1038/s41586-019-1534-3 · Cited by 524 · see citing works
Beerman, I., Bock, C., Garrison, B. S., Smith, Z. D., Gu, H., Meissner, A., & Rossi, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.017 · Cited by 485 · see citing works
Self-citationWilson, N. K., Kent, D. G., Buettner, F., Shehata, M., Macaulay, I. C., Calero-Nieto, F. J., Sánchez Castillo, M., Oedekoven, C. A., Diamanti, E., Schulte, R., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.04.004 · Cited by 466 · see citing works
Matsumoto, H., Kiryu, H., Furusawa, C., Ko, M. S. H., Ko, S. B. H., Gouda, N., Hayashi, T., & Nikaido, I. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx194 · Cited by 439 · see citing works
Russler-Germain, D. A., Spencer, D. H., Young, M. A., Lamprecht, T. L., Miller, C. A., Fulton, R., Meyer, M. R., Erdmann-Gilmore, P., Townsend, R. R., Wilson, R. K., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.010 · Cited by 452 · see citing works
PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy
Hsu, J. I., Dayaram, T., Tovy, A., De Braekeleer, E., Jeong, M., Wang, F., Zhang, J., Heffernan, T. P., Gera, S., Kovacs, J. J., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.10.004 · Cited by 425 · see citing works
Sano, S., Oshima, K., Wang, Y., Katanasaka, Y., Sano, M., & Walsh, K. (2018) · Circulation Research · doi:10.1161/circresaha.118.313225 · Cited by 417 · see citing works
Buscarlet, M., Provost, S., Zada, Y. F., Barhdadi, A., Bourgoin, V., Lépine, G., Mollica, L., Szuber, N., Dubé, M.-P., & Busque, L. (2017) · Blood · doi:10.1182/blood-2017-04-777029 · Cited by 383 · see citing works
Goodell, M. A., & Rando, T. A. (2015) · Science · doi:10.1126/science.aab3388 · Cited by 347 · see citing works
Self-citationChronic infection drives Dnmt3a-loss-of-function clonal hematopoiesis via IFNγ signaling
Hormaechea-Agulla, D., Matatall, K. A., Le, D. T., Kain, B., Long, X., Kus, P., Jaksik, R., Challen, G. A., Kimmel, M., & King, K. Y. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.03.002 · Cited by 329 · see citing works
Self-citationMetabolic regulation of stem cell function in tissue homeostasis and organismal ageing
Chandel, N. S., Jasper, H., Ho, T. T., & Passegué, E. (2016) · Nature Cell Biology · doi:10.1038/ncb3385 · Cited by 326 · see citing works
Age-related clonal hematopoiesis
Shlush, L. I. (2018) · Blood · doi:10.1182/blood-2017-07-746453 · Cited by 281 · see citing works
Cellular and epigenetic drivers of stem cell ageing
Ermolaeva, M., Neri, F., Ori, A., & Rudolph, K. L. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0020-3 · Cited by 272 · see citing works
Guryanova, O. A., Shank, K., Spitzer, B., Luciani, L., Koche, R. P., Garrett-Bakelman, F. E., Ganzel, C., Durham, B. H., Mohanty, A., Hoermann, G., et al. (2016) · Nature Medicine · doi:10.1038/nm.4210 · Cited by 256 · see citing works
Loss of Dnmt3a Immortalizes Hematopoietic Stem Cells In Vivo
Jeong, M., Park, H. J., Celik, H., Ostrander, E. L., Reyes, J. M., Guzman, A., Rodriguez, B., Lei, Y., Lee, Y., Ding, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.025 · Cited by 243 · see citing works
Self-citationDnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation
Mayle, A., Yang, L., Rodriguez, B., Zhou, T., Chang, E., Curry, C. V., Challen, G. A., Li, W., Wheeler, D., Rebel, V. I., et al. (2015) · Blood · doi:10.1182/blood-2014-08-594648 · Cited by 235 · see citing works
Self-citationChronic immune response dysregulation in MDS pathogenesis
Barreyro, L., Chlon, T. M., & Starczynowski, D. T. (2018) · Blood · doi:10.1182/blood-2018-03-784116 · Cited by 226 · see citing works
Role of donor clonal hematopoiesis in allogeneic hematopoietic stem-cell transplantation
Frick, M., Chan, W., Arends, C. M., Hablesreiter, R., Halik, A., Heuser, M., Michonneau, D., Blau, O., Hoyer, K., Christen, F., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2018.79.2184 · Cited by 223 · see citing works
Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein
Lei, Y., Zhang, X., Su, J., Jeong, M., Gundry, M. C., Huang, Y.-H., Zhou, Y., Li, W., & Goodell, M. A. (2017) · Nature Communications · doi:10.1038/ncomms16026 · Cited by 218 · see citing works
Self-citationNutrient-sensing pathways and metabolic regulation in stem cells
Ochocki, J. D., & Simon, M. C. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201303110 · Cited by 140 · see citing works
<i>Dnmt3a</i> restrains mast cell inflammatory responses
Leoni, C., Montagner, S., Rinaldi, A., Bertoni, F., Polletti, S., Balestrieri, C., & Monticelli, S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616420114 · Cited by 138 · see citing works
Clonal Hematopoiesis: Mechanisms Driving Dominance of Stem Cell Clones
Challen, G., & Goodell, M. A. (2020) · Blood · doi:10.1182/blood.2020006510 · Cited by 131 · see citing works
Self-citationClonal hematopoiesis: Mutation-specific adaptation to environmental change
Florez, M. A., Tran, B. T., Wathan, T. K., DeGregori, J., Pietras, E. M., & King, K. Y. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.05.006 · Cited by 129 · see citing works
Telomere Dysfunction Drives Aberrant Hematopoietic Differentiation and Myelodysplastic Syndrome
Colla, S., Ong, D. S. T., Ogoti, Y., Marchesini, M., Mistry, N. A., Clise-Dwyer, K., Ang, S. A., Storti, P., Viale, A., Giuliani, N., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.007 · Cited by 105 · see citing works
Hogart, A., Lichtenberg, J., Ajay, S. S., Anderson, S., NIH Intramural Sequencing Center, Margulies, E. H., & Bodine, D. M. (2012) · Genome Research · doi:10.1101/gr.132878.111 · Cited by 101 · see citing works
Celik, H., Mallaney, C., Kothari, A., Ostrander, E. L., Eultgen, E., Martens, A., Miller, C. A., Hundal, J., Klco, J. M., & Challen, G. A. (2015) · Blood · doi:10.1182/blood-2014-08-594564 · Cited by 95 · see citing works
Self-citationMolecular Pathophysiology of Myelodysplastic Syndromes
Lindsley, R. C., & Ebert, B. L. (2013) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-132436 · Cited by 88 · see citing works
Cole, C. B., Russler-Germain, D. A., Ketkar, S., Verdoni, A. M., Smith, A. M., Bangert, C. V., Helton, N. M., Guo, M., Klco, J. M., O’Laughlin, S., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci93041 · Cited by 84 · see citing works
Clonal hematopoiesis and inflammation – the perpetual cycle
Avagyan, S., & Zon, L. I. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.12.001 · Cited by 79 · see citing works
Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis
Natarajan, P., Jaiswal, S., & Kathiresan, S. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.118.001926 · Cited by 63 · see citing works
Tovy, A., Reyes, J. M., Gundry, M. C., Brunetti, L., Lee-Six, H., Petljak, M., Park, H. J., Guzman, A. G., Rosas, C., Jeffries, A. R., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.06.018 · Cited by 30 · see citing works
Self-citation<i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i>
Zhang, C. R., Ostrander, E. L., Kukhar, O., Mallaney, C., Sun, J., Haussler, E., Celik, H., Koh, W. K., King, K. Y., Gontarz, P., et al. (2022) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-21-0132 · Cited by 23 · see citing works
Self-citationKopp, K., Silva, P., Damm, F., & Cosma, N. C. (2026) · Biomedicines · doi:10.3390/biomedicines14051012
- Authors
- Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., Liang, S., Lu, Y., Darlington, G. J., Meissner, A., Issa, J.-P. J., Godley, L. A., Li, W., & Goodell, M. A.
- Affiliations
- Baylor College of Medicine (US)
- University of North Carolina at Chapel Hill (US)
- Broad Institute (US)
- University of Chicago (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Li, Wei
- Goodell, Margaret A
- ORCID
- Venue
- Nature Genetics
- Published
- 2011-12-04
- Volume
- 44
- Issue
- 1
- Pages
- 23-31
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3637952
- OpenAlex
- W2041191257
- Cited by
- 1,122
- References
- 49
- Citations by year
- 2026: 39 · 2025: 64 · 2024: 61 · 2023: 63 · 2022: 82 · 2021: 87 · 2020: 91 · 2019: 62 · 2018: 72 · 2017: 73 · 2016: 108 · 2015: 89 · 2014: 105 · 2013: 70 · 2012: 53
- FWCI
- 49.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG036562, RC2AG036562)
- National Heart, Lung, and Blood Institute (F32HL086223, HL086223)
- National Cancer Institute (P50CA100632, CA100632, K25CA123344, CA125123, R01CA129831, CA129831, P30CA125123, P50CA126752)
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK084259, DK092883, R56DK092883, R01DK058192, R00DK084259, DK58192, R01DK092883, P30DK056338)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- DNMT3A, DNMT3B, hematopoietic stem cells, hematopoietic stem cell differentiation, DNA methylation, epigenetic silencing, conditional gene deletion, CpG island hypermethylation, global DNA hypomethylation, serial transplantation, bone marrow, embryonic stem cells
- MeSH terms
- DNA Methyltransferase 3A, Animals, Cell Differentiation, Cell Division, DNA (Cytosine-5-)-Methyltransferases, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Mutation, Mice, Knockout, DNA Methylation, Mice
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