ArticleNature2013
Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.
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Who cites it
192 citing papers in PubMed, 1 synthesis or guideline pooled it, 292 citations in OpenAlex.
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- Revisiting heritability accounting for shared environmental effects and maternal inheritance.Human genetics · 2015Trial
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- Plagl1 regulates the retinal progenitor cell to Müller glial cell transition.PLoS genetics · 2026Article
- Identifying lncRNA-Protein Interactions in Hematopoietic Progenitor Cells by Hybridization Capture and Mass Spectrometry.Journal of proteome research · 2025Article
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- Biological functions and affected signaling pathways by Long Non-Coding RNAs in the immune system.Non-coding RNA research · 2025Review
- Noncoding RNAs as regulators of FOSL1 in cancer.Frontiers in immunology · 2025Review
- The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- LUCAT1-Mediated Competing Endogenous RNA (ceRNA) Network in Triple-Negative Breast Cancer.Cells · 2024Article
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- M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression via miR-520g-3p/SMIM22/GALE axis.NPJ precision oncology · 2024Article
- Association ofMolecular genetics and metabolism reports · 2024Article
- Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.Cell communication and signaling : CCS · 2024Article
- Pivotal functions and impact of long con-coding RNAs on cellular processes and genome integrity.Journal of biomedical science · 2024Review
- Identification of IGF2 promotes skin wound healing by co-expression analysis.International wound journal · 2024Article
132 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.