Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence
Open accessAbstract
The epigenetic regulation of imprinted genes by monoallelic DNA methylation of either maternal or paternal alleles is critical for embryonic growth and development. Imprinted genes were recently shown to be expressed in mammalian adult stem cells to support self-renewal of neural and lung stem cells; however, a role for imprinting per se in adult stem cells remains elusive. Here we show upregulation of growth-restricting imprinted genes, including in the H19-Igf2 locus, in long-term haematopoietic stem cells and their downregulation upon haematopoietic stem cell activation and proliferation. A differentially methylated region upstream of H19 (H19-DMR), serving as the imprinting control region, determines the reciprocal expression of H19 from the maternal allele and Igf2 from the paternal allele. In addition, H19 serves as a source of miR-675, which restricts Igf1r expression. We demonstrate that conditional deletion of the maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell quiescence, a state required for long-term maintenance of haematopoietic stem cells, and compromises haematopoietic stem cell function. Maternal-specific H19-DMR deletion results in activation of the Igf2-Igfr1 pathway, as shown by the translocation of phosphorylated FoxO3 (an inactive form) from nucleus to cytoplasm and the release of FoxO3-mediated cell cycle arrest, thus leading to increased activation, proliferation and eventual exhaustion of haematopoietic stem cells. Mechanistically, maternal-specific H19-DMR deletion leads to Igf2 upregulation and increased translation of Igf1r, which is normally suppressed by H19-derived miR-675. Similarly, genetic inactivation of Igf1r partly rescues the H19-DMR deletion phenotype. Our work establishes a new role for this unique form of epigenetic control at the H19-Igf2 locus in maintaining adult stem cells.
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Loss of H19-mediated repression of Igf2 leads to hematopoietic stem cell exhaustion.
“Quiescence is key to maintaining this stem cell population, and the loss of H19-mediated repression of Igf2 leads to hematopoietic stem cell exhaustion (Venkatraman et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Venkatraman et al., 2013
H19-mediated repression of Igf2 is important for maintenance of hematopoietic stem cell quiescence.
“Furthermore, H19-mediated repression of Igf2 has been demonstrated to be important for the maintenance of hematopoietic stem cell quiescence (Venkatraman et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Venkatraman et al., 2013
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Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556 · see citing works
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Irizarry, R. A. (2003) · Biostatistics · doi:10.1093/biostatistics/4.2.249 · Cited by 10,603 · see citing works
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,185 · see citing works
Summaries of Affymetrix GeneChip probe level data
Irizarry, R. A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng015 · Cited by 4,837 · see citing works
Identification of the haematopoietic stem cell niche and control of the niche size
Zhang, J., Niu, C. S., Ye, L., Huang, H., He, X. C., Tong, W.-G., Ross, J., Haug, J., Johnson, T. J., Feng, J. Q., et al. (2003) · Nature · doi:10.1038/nature02041 · Cited by 2,948 · see citing works
Self-citationParental imprinting of the mouse insulin-like growth factor II gene
DeChiara, T. M., Robertson, E. J., & Efstratiadis, A. (1991) · Cell · doi:10.1016/0092-8674(91)90513-x · Cited by 1,795 · see citing works
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562 · see citing works
The <i>let-7</i> MicroRNA Represses Cell Proliferation Pathways in Human Cells
Johnson, C. D., Esquela-Kerscher, A., Stefani, G., Byrom, M., Kelnar, K., Ovcharenko, D., Wilson, M., Wang, X., Shelton, J., Shingara, J., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1083 · Cited by 1,224 · see citing works
Zhao, Z., Tavoosidana, G., Sjölinder, M., Göndör, A., Mariano, P., Wang, S., Kanduri, C., Lezcano, M., Sandhu, K. S., Singh, U., et al. (2006) · Nature Genetics · doi:10.1038/ng1891 · Cited by 957 · see citing works
PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention
Zhang, J., Grindley, J. C., Yin, T., Jayasinghe, S., He, X. C., Ross, J. T., Haug, J. S., Rupp, D., Porter-Westpfahl, K. S., Wiedemann, L. M., et al. (2006) · Nature · doi:10.1038/nature04747 · Cited by 817 · see citing works
Self-citationThe H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r
Keniry, A., Oxley, D., Monnier, P., Kyba, M., Dandolo, L., Smits, G., & Reik, W. (2012) · Nature Cell Biology · doi:10.1038/ncb2521 · Cited by 806 · see citing works
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells
Stadtfeld, M., Apostolou, E., Akutsu, H., Fukuda, A., Follett, P., Natesan, S., Kono, T., Shioda, T., & Hochedlinger, K. (2010) · Nature · doi:10.1038/nature09017 · Cited by 801 · see citing works
Yang, L., Bryder, D., Adolfsson, J., Nygren, J., Månsson, R., Sigvardsson, M., & Jacobsen, S. E. W. (2004) · Blood · doi:10.1182/blood-2004-06-2159 · Cited by 469 · see citing works
Zac1 Regulates an Imprinted Gene Network Critically Involved in the Control of Embryonic Growth
Varrault, A., Gueydan, C., Delalbre, A., Bellmann, A., Houssami, S., Aknin, C., Séverac, D., Chotard, L., Kahli, M., Digarcher, A. L., et al. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.09.003 · Cited by 467 · see citing works
Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment
Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E., & Orkin, S. H. (2007) · Cell · doi:10.1016/j.cell.2007.03.055 · Cited by 424 · see citing works
Akashi, K., He, X., Chen, J., Iwasaki, H., Niu, C. S., Steenhard, B. M., Zhang, J., Haug, J., & Li, L. (2002) · Blood · doi:10.1182/blood-2002-06-1780 · Cited by 368 · see citing works
Self-citationPostnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis
Ferrón, S. R., Charalambous, M., Radford, E. J., McEwen, K. R., Wildner, H., Hind, E., Morante‐Redolat, J. M., Laborda, J., Guillemot, F., Bauer, S. R., et al. (2011) · Nature · doi:10.1038/nature10229 · Cited by 294 · see citing works
Noncanonical Wnt Signaling Maintains Hematopoietic Stem Cells in the Niche
Sugimura, R., He, X., Venkatraman, A., Arai, F., Box, A., Semerad, C. L., Haug, J. S., Peng, L., Zhong, X.-B., Suda, T., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.041 · Cited by 292 · see citing works
Self-citationZou, P., Yoshihara, H., Hosokawa, K., Tai, I., Shinmyozu, K., Tsukahara, F., Maru, Y., Nakayama, K., Nakayama, K. I., & Suda, T. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.07.003 · Cited by 289 · see citing works
Miller, C., & Eaves, C. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13648 · Cited by 261 · see citing works
Genomic imprinting: employing and avoiding epigenetic processesPreprint
Bartolomei, M. S. (2009) · Genes & Development · doi:10.1101/gad.1841409 · Cited by 251 · see citing works
Self-citationThe Importance of Imprinting in the Human Placenta
Frost, J. M., & Moore, G. E. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001015 · Cited by 247 · see citing works
5-Fluorouracil spares hemopoietic stem cells responsible for long-term repopulation.
Lerner, C. P., & Harrison, D. E. (1990) · PubMed · Cited by 246 · see citing works
Regulation of growth and metabolism by imprinted genes
Smith, F. M., Garfield, A. S., & Ward, A. (2006) · Cytogenetic and Genome Research · doi:10.1159/000090843 · Cited by 196 · see citing works
Perry, J. M., He, X., Sugimura, R., Grindley, J. C., Haug, J. S., Ding, S., & Li, L. (2011) · Genes & Development · doi:10.1101/gad.17421911 · Cited by 188 · see citing works
Self-citationAdult mouse hematopoietic stem cells: purification and single-cell assays
Ema, H., Morita, Y., Yamazaki, S., Matsubara, A., Seita, J., Tadokoro, Y., Kondo, H., Takano, H., & Nakauchi, H. (2006) · Nature Protocols · doi:10.1038/nprot.2006.447 · Cited by 184 · see citing works
The let-7–Imp axis regulates ageing of the Drosophila testis stem-cell niche
Toledano, H., D’Alterio, C., Czech, B., Levine, E., & Jones, D. L. (2012) · Nature · doi:10.1038/nature11061 · Cited by 178 · see citing works
N-Cadherin Expression Level Distinguishes Reserved versus Primed States of Hematopoietic Stem Cells
Haug, J. S., He, X., Grindley, J. C., Wunderlich, J. P., Gaudenz, K., Ross, J. T., Paulson, A., Wagner, K. P., Xie, Y., Zhu, R., et al. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.01.017 · Cited by 156 · see citing works
Self-citationConditional mutagenesis in mice with heat shock promoter-driven cre transgenes
Dietrich, P., Dragatsis, I., Xuan, S., Zeitlin, S. O., & Efstratiadis, A. (2000) · Mammalian Genome · doi:10.1007/s003350010037 · Cited by 131 · see citing works
Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci
Zacharek, S. J., Brainson, C. F., Lau, A. N., Gludish, D. W., Chou, A. Y., Ho, J. W. K., Zamponi, R., Gazit, R., Bock, C., Jäger, N., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.07.007 · Cited by 129 · see citing works
Smad4 is critical for self-renewal of hematopoietic stem cells
Karlsson, G., Blank, U., Moody, J. L., Ehinger, M., Singbrant, S., Deng, C., & Karlsson, S. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20060465 · Cited by 125 · see citing works
Yu, W., Imoto, I., Inoue, J., Onda, M., Emi, M., & Inazawa, J. (2006) · Oncogene · doi:10.1038/sj.onc.1209899 · Cited by 103 · see citing works
Igf1r as a therapeutic target in a mouse model of basal-like breast cancer
Klinakis, A., Szabolcs, M. J., Chen, G., Xuan, S., Hibshoosh, H. H., & Efstratiadis, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810221106 · Cited by 100 · see citing works
Imprinted Genes That Regulate Early Mammalian Growth Are Coexpressed in Somatic Stem Cells
Berg, J. S., Lin, K. K., Sonnet, C., Boles, N. C., Weksberg, D. C., Nguyen, H., Holt, L. J., Rickwood, D., Daly, R. J., & Goodell, M. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026410 · Cited by 84 · see citing works
Niedernberg, A., Tunaru, S., Blaukat, A., Ardati, A., & Kostenis, E. (2003) · Cellular Signalling · doi:10.1016/s0898-6568(02)00119-5 · Cited by 72 · see citing works
Genomic imprinting mechanisms in embryonic and extraembryonic mouse tissues
Hudson, Q. J., Kuliński, T. M., Huetter, S. P., & Barlow, D. P. (2010) · Heredity · doi:10.1038/hdy.2010.23 · Cited by 69 · see citing works
Thorvaldsen, J. L., Fedoriw, A., Nguyen, S. C., & Bartolomei, M. S. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.4.1245-1258.2006 · Cited by 55 · see citing works
Self-citationNecdin restricts proliferation of hematopoietic stem cells during hematopoietic regeneration
Kubota, Y., Osawa, M., Jakt, L. M., Yoshikawa, K., & Nishikawa, S. (2009) · Blood · doi:10.1182/blood-2009-07-230292 · Cited by 51 · see citing works
Smad signal transduction : Smads in proliferation, differentiation and disease
ten Dijke, P., & Heldin, C. (2006) · Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) · doi:10.1007/1-4020-4709-6 · Cited by 19 · see citing works
Kang, H. M., Park, S. H., & Kim, H. (2011) · Cell Proliferation · doi:10.1111/j.1365-2184.2011.00755.x · Cited by 7 · see citing works
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Research works printed but not linked: 2
- [31]Thorvaldsen JL Fedoriw AM Nguyen S Bartolomei MS Developmental profile of H19 differentially methylated domain (DMD) deletion alleles reveals multiple roles of the DMD in regulating allelic expression and DNA methylation at the imprinted H19/Igf2 locus Molecular and cellular biology 26 1245 1258 2006 16449639 PMC1367202
- [34]Haug JS N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells Cell stem cell 2 367 379 2008 18397756
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Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.13 · Cited by 878 · see citing works
Gene regulation in the immune system by long noncoding RNAs
Chen, Y. G., Satpathy, A. T., & Chang, H. Y. (2017) · Nature Immunology · doi:10.1038/ni.3771 · Cited by 686 · see citing works
Ren, J., Ding, L., Zhang, D., Shi, G., Xu, Q., Shen, S., Wang, Y., Wang, T., & Hou, Y. (2018) · Theranostics · doi:10.7150/thno.25541 · Cited by 698 · see citing works
Cabezas-Wallscheid, N., Klimmeck, D., Hansson, J., Lipka, D., Reyes, A., Wang, Q., Weichenhan, D., Lier, A., von Paleske, L., Renders, S., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.07.005 · Cited by 352 · see citing works
Raveh, E., Matouk, I., Gilon, M., & Hochberg, A. (2015) · Molecular Cancer · doi:10.1186/s12943-015-0458-2 · Cited by 503 · see citing works
Booth, L. N., & Brunet, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.013 · Cited by 499 · see citing works
Cheng, C., Adams, G. B., Perin, L., Wei, M., Zhou, X., Lam, B. S., Sacco, S. D., Mirisola, M. G., Quinn, D. I., Dorff, T. B., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.04.014 · Cited by 484 · see citing works
Dey, B. K., Pfeifer, K. E., & Dutta, A. (2014) · Genes & Development · doi:10.1101/gad.234419.113 · Cited by 483 · see citing works
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Peters, J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3766 · Cited by 432 · see citing works
Weischenfeldt, J., Dubash, T., Drainas, A. P., Mardin, B. R., Chen, Y., Stütz, A. M., Waszak, S. M., Bosco, G., Halvorsen, A. R., Raeder, B., et al. (2017) · Nature Genetics · doi:10.1038/ng.3722 · Cited by 404 · see citing works
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Xing, C., Sun, S., Yue, Z.-Q., & Bai, F. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111158 · Cited by 328 · see citing works
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Li, J., Meng, H., Bai, Y., & Wang, K. (2016) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504016x14549667334007 · Cited by 301 · see citing works
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Gao, Y., Wu, F., Zhou, J., Yan, L., Jurczak, M. J., Lee, H., Yang, L., Mueller, M., Zhou, X., Dandolo, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1160 · Cited by 269 · see citing works
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Zhou, J., Yang, L., Zhong, T., Mueller, M., Men, Y., Zhang, N., Xie, J., Giang, K., Chung, H., Sun, X., et al. (2015) · Nature Communications · doi:10.1038/ncomms10221 · Cited by 254 · see citing works
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Park, E.-G., Pyo, S.-J., Cui, Y., Yoon, S.-H., & Nam, J. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab504 · Cited by 252 · see citing works
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Peng, F., Li, T., Wang, K.-L., Xiao, G.-Q., Wang, J.-H., Zhao, H.-D., Kang, Z.-J., Fan, W., Zhu, L.-L., Li, M., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2016.438 · Cited by 244 · see citing works
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Sun, W., Yang, Y., Xu, C., & Guo, J. (2017) · Cancer Genetics · doi:10.1016/j.cancergen.2017.06.003 · Cited by 206 · see citing works
Qian, P., He, X., Paulson, A., Li, Z., Fang, T., Perry, J. M., Guo, F., Zhao, M. L., Zhi, L., Venkatraman, A., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.11.001 · Cited by 199 · see citing works
Self-citationGhazal, S., McKinnon, B. D., Zhou, J., Mueller, M., Men, Y., Yang, L., Mueller, M. D., Flannery, C. A., Huang, Y., & Taylor, H. S. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201505245 · Cited by 193 · see citing works
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Geng, H., Bu, H., Liu, F., Wu, L., Pfeifer, K. E., Chou, P. M., Wang, X., Sun, J., Lu, L., Pandey, A., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.03.058 · Cited by 183 · see citing works
Self-citationEmerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis
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Luo, M., Jeong, M., Sun, D., Park, H. J., Rodriguez, B. A. T., Xia, Z., Yang, L., Zhang, X., Sheng, K., Darlington, G., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.02.002 · Cited by 172 · see citing works
Dong, S., Qu, X., Li, W., Zhong, X., Li, P., Yang, S., Chen, X., Shao, M., & Zhang, L. (2015) · Journal of Hematology & Oncology · doi:10.1186/s13045-015-0140-6 · Cited by 166 · see citing works
Self-citationMirzaei, S., Paskeh, M. D. A., Okina, E., Gholami, M. H., Hushmandi, K., Hashemi, M., Kalu, A., Zarrabi, A., Nabavi, N., Rabiee, N., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02406-1 · Cited by 166 · see citing works
Song, Y., Liu, C., Liu, X., Trottier, J., Beaudoin, M., Zhang, L. R., Pope, C. A., Peng, G., Barbier, O., Zhong, X., et al. (2017) · Hepatology · doi:10.1002/hep.29209 · Cited by 152 · see citing works
Self-citationZhao, M., Tao, F., Venkatraman, A., Li, Z., Smith, S. E., Unruh, J., Chen, S., Ward, C., Qian, P., Perry, J. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.093 · Cited by 146 · see citing works
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Ohtsuka, M., Ling, H. Y., Ivan, C., Pichler, M., Matsushita, D., Goblirsch, M. J., Stiegelbauer, V., Shigeyasu, K., Zhang, X., Chen, M., et al. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.10.026 · Cited by 113 · see citing works
Dignum, T., Varnum‐Finney, B., Srivatsan, S. R., Dozono, S., Waltner, O. G., Heck, A. M., Ishida, T., Nourigat-Mckay, C., Jackson, D. L., Rafii, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109675 · Cited by 112 · see citing works
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Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets
Luan, Y., Zhu, X., Jiao, Y., Liu, H., Huang, Z., Pei, J., Xu, Y., Yang, Y., & Ren, K. (2024) · Cell Death Discovery · doi:10.1038/s41420-023-01792-5 · Cited by 106 · see citing works
Long Noncoding RNAs in Acute Myeloid Leukemia: Functional Characterization and Clinical Relevance
Gourvest, M., Brousset, P., & Bousquet, M. (2019) · Cancers · doi:10.3390/cancers11111638 · Cited by 107 · see citing works
The Implications of the Long Non-Coding RNA NEAT1 in Non-Cancerous Diseases
Prinz, F., Kapeller, A., Pichler, M., & Klec, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030627 · Cited by 102 · see citing works
Regulatory roles of long noncoding RNAs implicated in cancer hallmarks
Wang, J., Zhang, X., Chen, W., Hu, X., Li, J., & Liu, C. (2019) · International Journal of Cancer · doi:10.1002/ijc.32277 · Cited by 101 · see citing works
Zhou, J. R., Xu, J., Zhang, L., Liu, S., Ma, Y., Wen, X., Hao, J., Li, Z., Ni, Y., Li, X., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2018.11.023 · Cited by 98 · see citing works
Self-citationRatajczak, M. Z., Zuba‐Surma, E. K., Wojakowski, W., Suszyńska, M., Mierzejewska, K., Liu, R., Ratajczak, J., Shin, D., & Kucia, M. (2013) · Leukemia · doi:10.1038/leu.2013.255 · Cited by 100 · see citing works
Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer
Klymenko, Y., Kim, O., & Stack, M. (2017) · Cancers · doi:10.3390/cancers9080104 · Cited by 99 · see citing works
Mierzejewska, K., Borkowska, S., Suszyńska, E., Suszyńska, M., Poniewierska-Baran, A., Maj, M. A., Pędziwiatr, D., Adamiak, M., Abdel‐Latif, A., Kakar, S. S., et al. (2015) · Stem Cells and Development · doi:10.1089/scd.2014.0546 · Cited by 95 · see citing works
miR675 upregulates long noncoding RNA H19 through activating EGR1 in human liver cancer
Li, H., Li, J., Jia, S., Wu, M., An, J., Zheng, Q., Zhang, W., & Lu, D. (2015) · Oncotarget · doi:10.18632/oncotarget.5579 · Cited by 94 · see citing works
Self-citationRegulation and function of insulin and insulin-like growth factor receptor signalling
Choi, E., Duan, C., & Bai, X. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00826-3 · Cited by 93 · see citing works
Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity
Zeng, W., Jiang, S., Kong, X., El-Ali, N. C., Ball, A. R., I-Hsing, C., Hashimoto, N., Yokomori, K., & Mortazavi, A. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw739 · Cited by 91 · see citing works
Adhami, H. A., Evano, B., Digarcher, A. L., Gueydan, C., Dubois, E., Parrinello, H., Dantec, C., Bouschet, T., Varrault, A., & Journot, L. (2015) · Genome Research · doi:10.1101/gr.175919.114 · Cited by 92 · see citing works
Noncoding RNA control of cellular senescence
Abdelmohsen, K., & Gorospe, M. (2015) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1297 · Cited by 90 · see citing works
Epigenetics of myelodysplastic syndromes
Itzykson, R., & Fenaux, P. (2013) · Leukemia · doi:10.1038/leu.2013.343 · Cited by 90 · see citing works
The role of long non-coding RNAs in rheumatic diseases
Tang, Y., Zhou, T., Yu, X., Xue, Z., & Shen, N. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.162 · Cited by 89 · see citing works
Understanding of leukemic stem cells and their clinical implications
Wang, X., Huang, S., & Chen, J. (2017) · Molecular Cancer · doi:10.1186/s12943-016-0574-7 · Cited by 90 · see citing works
Long Non-Coding RNAs: The Key Players in Glioma Pathogenesis
Kiang, K. M. Y., Zhang, X., & Leung, G. (2015) · Cancers · doi:10.3390/cancers7030843 · Cited by 85 · see citing works
H19 controls reactivation of the imprinted gene network during muscle regeneration
Martinet, C., Monnier, P., Louault, Y., Bénard, M., Gabory, A., & Dandolo, L. (2016) · Development · doi:10.1242/dev.131771 · Cited by 85 · see citing works
Chaker, Z., Aïd, S., Berry, H., & Holzenberger, M. (2015) · Aging Cell · doi:10.1111/acel.12365 · Cited by 80 · see citing works
CUDR promotes liver cancer stem cell growth through upregulating TERT and C-Myc
Pu, H., Zheng, Q., Li, H., Wu, M., An, J., Gui, X., Li, T., & Lu, D. (2015) · Oncotarget · doi:10.18632/oncotarget.5805 · Cited by 83 · see citing works
Self-citationLong non-coding RNAs in glioma: Functional roles and clinical perspectives
Zhang, X., & Leung, G. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.05.008 · Cited by 81 · see citing works
Zhao, Y., Chen, M., Lian, D., Li, Y., Li, Y., Wang, J., Deng, S., Yu, K., & Lian, Z. (2019) · Cells · doi:10.3390/cells8090988 · Cited by 77 · see citing works
MiRNAs Derived from Cancer-Associated Fibroblasts in Colorectal Cancer
Savardashtaki, A., Shabaninejad, Z., Movahedpour, A., Sahebnasagh, R., Mirzaei, H., & Hamblin, M. R. (2019) · Epigenomics · doi:10.2217/epi-2019-0110 · Cited by 79 · see citing works
Hu, M., Zeng, H., Chen, S., Xu, Y., Wang, S., Tang, Y., Wang, X., Du, C., Shen, M., Chen, F., et al. (2018) · Blood · doi:10.1182/blood-2018-02-831669 · Cited by 76 · see citing works
Epigenetic regulation of hematopoietic stem cell aging
Beerman, I., & Rossi, D. J. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.09.013 · Cited by 72 · see citing works
LncRNAs and Immunity: Coding the Immune System with Noncoding Oligonucleotides
Bocchetti, M., Scrima, M., Melisi, F., Luce, A., Sperlongano, R., Caraglia, M., Zappavigna, S., & Cossu, A. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041741 · Cited by 68 · see citing works
Zuckerwise, L. C., Li, J., Lu, L., Men, Y., Geng, T., Buhimschi, C. S., Buhimschi, I. A., Bukowski, R. K., Guller, S. M., Paidas, M. J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9534 · Cited by 70 · see citing works
IGF2: A Role in Metastasis and Tumor Evasion from Immune Surveillance?
Belfiore, A., Rapicavoli, R. V., Moli, R. L., Lappano, R., Morrione, A., Francesco, E. M. D., & Vella, V. (2023) · Biomedicines · doi:10.3390/biomedicines11010229 · Cited by 64 · see citing works
Li, F., Ma, N., Zhao, R., Wu, G., Zhang, Y., Qiao, Y., Han, D. H., Xu, Y. F., Xiang, Y., Yan, B., et al. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12293 · Cited by 60 · see citing works
Zaro, B. W., Noh, J. J., Mascetti, V. L., Demeter, J., George, B. M., Żukowska, M., Gulati, G. S., Sinha, R., Flynn, R. A., Banuelos, A. M., et al. (2020) · eLife · doi:10.7554/elife.62210 · Cited by 56 · see citing works
IGF-1 facilitates thrombopoiesis primarily through Akt activation
Chen, S., Hu, M., Shen, M., Wang, S., Wang, C., Chen, F., Tang, Y., Wang, X., Zeng, H., Chen, M., et al. (2018) · Blood · doi:10.1182/blood-2018-01-825927 · Cited by 59 · see citing works
Suo, M., Rommelfanger, M. K., Chen, Y., Amro, E. M., Han, B., Chen, Z., Szafranski, K., Chakkarappan, S. R., Boehm, B. O., MacLean, A. L., et al. (2022) · Blood · doi:10.1182/blood.2021012197 · Cited by 57 · see citing works
The Role of Long Non-coding RNAs in the Pathogenesis of RA, SLE, and SS
Gao, Y., Li, S., Zhang, Z., Yu, X., & Zheng, J. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00193 · Cited by 56 · see citing works
Shaikh, A., Bhartiya, D., Kapoor, S., & Nimkar, H. (2016) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0311-6 · Cited by 56 · see citing works
Yang, B., Jiao, B., Ge, W., Zhang, X., Wang, S., Zhao, H., & Wang, X. (2018) · BMC Genomics · doi:10.1186/s12864-018-4974-5 · Cited by 55 · see citing works
Goyal, N., Sivadas, A., Vellarikkal, S. K., Jayarajan, R., Verma, A., Sivasubbu, S., Scaria, V., & Datta, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-08281-7 · Cited by 56 · see citing works
Suszyńska, M., Zuba‐Surma, E. K., Maj, M. A., Mierzejewska, K., Ratajczak, J., Kucia, M., & Ratajczak, M. Z. (2013) · Stem Cells and Development · doi:10.1089/scd.2013.0472 · Cited by 54 · see citing works
Mammary gland stem cells and their application in breast cancer
Yang, X., Wang, H., & Jiao, B. (2016) · Oncotarget · doi:10.18632/oncotarget.12893 · Cited by 54 · see citing works
Maternal–fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer
Haig, D. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0178 · Cited by 53 · see citing works
Wang, F., He, J., Liu, S., Gao, A., Yang, L., Sun, G., Ding, W., Li, C., Gou, F., He, M., et al. (2021) · Blood · doi:10.1182/blood.2021011314 · Cited by 49 · see citing works
Self-citationQian, P., Kumar, B. D., He, X., Nolte, C., Gogol, M., Ahn, Y., Chen, S., Li, Z., Xu, H., Perry, J. M., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.04.012 · Cited by 51 · see citing works
Self-citationMolecular regulation of hematopoietic stem cell quiescence
Chen, Z., Guo, Q., Song, G., & Hou, Y. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04200-w · Cited by 49 · see citing works
Long noncoding RNAs during normal and malignant hematopoiesis
Alvarez‐Dominguez, J. R., Hu, W., Gromatzky, A. A., & Lodish, H. F. (2014) · International Journal of Hematology · doi:10.1007/s12185-014-1552-8 · Cited by 48 · see citing works
H19 derived microRNA-675 regulates cell proliferation and migration through CDK6 in glioma.
Li, C., Lei, B., Huang, S., Zheng, M., Liu, Z., Li, Z., & Deng, Y. (2015) · Europe PMC (PubMed Central) · Cited by 48 · see citing works
Lai, K., Jia, S., Yu, S., Luo, J., & He, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.18263 · Cited by 45 · see citing works
Pio, L., O'Neill, A. F., Woodley, H., Murphy, A. J., Tiao, G. M., Franchi‐Abella, S., Fresneau, B. C., Watanabe, K., Alaggio, R., Lopez-Terrada, D. H., et al. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00620-7 · Cited by 45 · see citing works
Multi-level remodeling of transcriptional landscapes in aging and longevity
Lai, R. W., Lu, R. J., Danthi, P. S., Bravo, J. I., Goumba, A., Sampathkumar, N. K., & Benayoun, B. A. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.1.296 · Cited by 42 · see citing works
Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque
Espinoza, D. A., Fan, X., Yang, D., Cordes, S., Truitt, L. L., Calvo, K. R., Yabe, I. M., Demirci, S., Hope, K. J., Hong, S. G., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.04.003 · Cited by 43 · see citing works
Role of miRNAs and lncRNAs in hematopoietic stem cell differentiation
Ghafouri‐Fard, S., Niazi, V., & Taheri, M. N. (2020) · Non-coding RNA Research · doi:10.1016/j.ncrna.2020.12.002 · Cited by 43 · see citing works
Pivotal functions and impact of long con-coding RNAs on cellular processes and genome integrity
Sharma, S., Houfani, A. A., & Foster, L. J. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01038-1 · Cited by 42 · see citing works
Ratajczak, M. Z., Bartke, A., & Darżynkiewicz, Z. (2017) · Stem Cell Reviews and Reports · doi:10.1007/s12015-017-9728-2 · Cited by 42 · see citing works
Wang, Y., Wei, J., Ma, W., Liang, C., Chai, H., & Tu, J. (2018) · Cancer Biomarkers · doi:10.3233/cbm-170781 · Cited by 40 · see citing works
Long noncoding RNAs: emerging regulators of normal and malignant hematopoiesis
Qiu, Y., Xu, M., & Huang, S. (2021) · Blood · doi:10.1182/blood.2021011992 · Cited by 39 · see citing works
Somatic mutations and epigenetic abnormalities in myelodysplastic syndromes
Itzykson, R., Kosmider, O., & Fenaux, P. (2013) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2014.01.001 · Cited by 38 · see citing works
Hu, M., Lu, Y., Wang, S., Zhang, Z., Qi, Y., Chen, N., Shen, M., Chen, F., Chen, M., Yang, L., et al. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00848-2 · Cited by 38 · see citing works
Goyal, N., Tiwary, S., Kesharwani, D., & Datta, M. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1718-6 · Cited by 37 · see citing works
Klimmeck, D., Cabezas‐Wallscheid, N., Reyes, A., von Paleske, L., Renders, S., Hansson, J., Krijgsveld, J., Huber, W. K., & Trumpp, A. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.08.012 · Cited by 36 · see citing works
Noncoding RNAs in Glioblastoma
Zhang, Y., Cruickshanks, N. A., Pahuski, M., Yuan, F., Dutta, A., Schiff, D., Purow, B. W., & Abounader, R. (2017) · Codon Publications eBooks · doi:10.15586/codon.glioblastoma.2017.ch6 · Cited by 38 · see citing works
Is There a Histone Code for Cellular Quiescence?
Bonitto, K., Sarathy, K., Atai, K., Mitra, M., & Coller, H. A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.739780 · Cited by 36 · see citing works
- Authors
- Venkatraman, A., He, X. C., Thorvaldsen, J. L., Sugimura, R., Perry, J. M., Tao, F., Zhao, M., Christenson, M. K., Sanchez, R., Yu, J. Y., Peng, L., Haug, J. S., Paulson, A., Li, H., Zhong, X.-B., Clemens, T. L., Bartolomei, M. S., & Li, L.
- Affiliations
- Stowers Institute for Medical Research (US)
- University of Pennsylvania (US)
- University of Kansas Medical Center (US)
- Johns Hopkins University (US)
- Corresponding author
- Li, Linheng
- ORCID
- Venue
- Nature
- Published
- 2013-07-17
- Volume
- 500
- Issue
- 7462
- Pages
- 345-349
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3896866
- OpenAlex
- W2081038378
- Cited by
- 296
- References
- 44
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 21 · 2023: 19 · 2022: 21 · 2021: 15 · 2020: 21 · 2019: 31 · 2018: 25 · 2017: 39 · 2016: 27 · 2015: 34 · 2014: 22 · 2013: 5
- FWCI
- 19.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM087376, GM-51279, R01GM051279, R37GM051279)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- genomic imprinting, hematopoietic stem cells, stem cell quiescence, H19 differentially methylated region, H19, insulin-like growth factor II, miR-675, IGF-1 receptor, FOXO3, DNA methylation
- MeSH terms
- Animals, Insulin-Like Growth Factor II, Signal Transduction, Transcriptional Activation, Receptor, IGF Type 1, Genomic Imprinting, Gene Expression Regulation, Developmental, Epigenesis, Genetic, Mice, Adult Stem Cells, RNA, Long Noncoding
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