ArticleCell stem cell2016
The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism.
Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 207 citations in OpenAlex.
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- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Mitochondria: the key hub for hematopoietic stem cell homeostasis maintenance and fate determination.Stem cell research & therapy · 2026Review
- Multiomic State-Transitions Reveal Post-Treatment Transcriptome Desynchronization in Acute Myeloid Leukemia.bioRxiv : the preprint server for biology · 2026Article
- DLK1 is a GATA1s-driven dependency and therapeutic target in Down syndrome-associated myeloid leukemia.Blood advances · 2026Article
- Transient mechanical activation of the Piezo1 channel facilitates ex vivo expansion of hematopoietic stem cells.Cell research · 2026Article
- Single-Cell Mitochondrial Lineage Tracing Decodes Fate Decision and Spatial Clonal Architecture in Human Hematopoietic Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bnip3lb-driven mitophagy maintains fate of the embryonic hematopoietic stem cell pool.Nature communications · 2026Article
- Activation of a branched-chain amino acid rheostat restores replication-dependent hematopoietic stem cell fitness.Cell stem cell · 2026Article
- Maternal acute SARS-CoV-2 infection impairs preimplantation embryo development and reprograms the early offspring hematopoietic system.Cell discovery · 2025Article
- Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia.Nature communications · 2025Article
- Ferumoxytol promotes haematopoietic stem cell post-injury regeneration as a reactive oxygen species scavenger.Nature nanotechnology · 2025Article
- Light and sex modifybioRxiv : the preprint server for biology · 2025Article
- SNORD113-114 cluster maintains haematopoietic stem cell self-renewal via orchestrating the translation machinery.Nature cell biology · 2025Article
- Silencing of maternally expressed RNAs in Dlk1-Dio3 domain causes fatal vascular injury in the fetal liver.Cellular and molecular life sciences : CMLS · 2024Article
- Autophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells.Cell stem cell · 2024Article
- Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.Cell communication and signaling : CCS · 2024Article
- Label-free metabolic optical biomarkers track stem cell fate transition in real time.Science advances · 2024Article
57 more citing papers are in PubMed but not listed here.
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18 authors at 7 institutions in 5 countries.
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Abstract
The mammalian imprinted Dlk1-Gtl2 locus produces multiple non-coding RNAs (ncRNAs) from the maternally inherited allele, including the largest miRNA cluster in the mammalian genome. This locus has characterized functions in some types of stem cell, but its role in hematopoietic stem cells (HSCs) is unknown. Here, we show that the Dlk1-Gtl2 locus plays a critical role in preserving long-term repopulating HSCs (LT-HSCs). Through transcriptome profiling in 17 hematopoietic cell types, we found that ncRNAs expressed from the Dlk1-Gtl2 locus are predominantly enriched in fetal liver HSCs and the adult LT-HSC population and sustain long-term HSC functionality. Mechanistically, the miRNA mega-cluster within the Dlk1-Gtl2 locus suppresses the entire PI3K-mTOR pathway. This regulation in turn inhibits mitochondrial biogenesis and metabolic activity and protects LT-HSCs from excessive reactive oxygen species (ROS) production. Our data therefore show that the imprinted Dlk1-Gtl2 locus preserves LT-HSC function by restricting mitochondrial metabolism.
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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.