ArticleBlood2021
Role of c-Myc haploinsufficiency in the maintenance of HSCs in mice.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Function and regulatory mechanism of RNA-binding protein IGF2BP2 in obesity and cancers.Molecular biology reports · 2026Review
- MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.Frontiers in immunology · 2026Review
- Targeting high-risk MYC-overexpressed osteosarcoma with an Aurora kinase inhibitor:--results from a pilot umbrella trial.NPJ precision oncology · 2025Article
- PDCD4: A critical regulator in leukemic signaling networks and its therapeutic potential.Molecular biology reports · 2025Review
- Cannabidiol restores hematopoietic stem cell stemness in mouse through Atf2-Lrp6 axis after acute irradiation.MedComm · 2025Article
- Article
- Chromosomal instability as a driver of cancer progression.Nature reviews. Genetics · 2025Review
- Exploring the contribution of Zfp521/ZNF521 on primary hematopoietic stem/progenitor cells and leukemia progression.Cell and tissue research · 2024Review
- Increased CCL2/CCR2 axis promotes tumor progression by increasing M2 macrophages in MYC/BCL2 double-expressor DLBCL.Blood advances · 2024Article
- MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.Signal transduction and targeted therapy · 2024Review
- Ing4-deficiency promotes a quiescent yet transcriptionally poised state in hematopoietic stem cells.iScience · 2024Article
- Trim47 prevents hematopoietic stem cell exhaustion during stress by regulating MAVS-mediated innate immune pathway.Nature communications · 2024Article
- A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.Genes & development · 2024Article
- α1,3-fucosylation treatment improves cord blood CD34 negative hematopoietic stem cell navigation.iScience · 2024Article
- Transcription Factor EB-Mediated Lysosomal Function Regulation for Determining Stem Cell Fate under Metabolic Stress.Molecules and cells · 2023Review
- Cordycepin (3'dA) Induces Cell Death of AC133Cancers · 2023Article
- Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity.Nature reviews. Molecular cell biology · 2023Review
- Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation.Leukemia · 2023Article
- The effects of MYC on tumor immunity and immunotherapy.Cell death discovery · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
This study was conducted to determine the dosage effect of c-Myc on hematopoiesis and its distinct role in mediating the Wnt/β-catenin pathway in hematopoietic stem cell (HSC) and bone marrow niche cells. c-Myc haploinsufficiency led to ineffective hematopoiesis by inhibiting HSC self-renewal and quiescence and by promoting apoptosis. We have identified Nr4a1, Nr4a2, and Jmjd3, which are critical for the maintenance of HSC functions, as previously unrecognized downstream targets of c-Myc in HSCs. c-Myc directly binds to the promoter regions of Nr4a1, Nr4a2, and Jmjd3 and regulates their expression. Our results revealed that Nr4a1 and Nr4a2 mediates the function of c-Myc in regulating HSC quiescence, whereas all 3 genes contribute to the function of c-Myc in the maintenance of HSC survival. Adenomatous polyposis coli (Apc) is a negative regulator of the Wnt/β-catenin pathway. We have provided the first evidence that Apc haploinsufficiency induces a blockage of erythroid lineage differentiation through promoting secretion of IL6 in bone marrow endothelial cells. We found that c-Myc haploinsufficiency failed to rescue defective function of Apc-deficient HSCs in vivo but it was sufficient to prevent the development of severe anemia in Apc-heterozygous mice and to significantly prolong the survival of those mice. Furthermore, we showed that c-Myc-mediated Apc loss induced IL6 secretion in endothelial cells, and c-Myc haploinsufficiency reversed the negative effect of Apc-deficient endothelial cells on erythroid cell differentiation. Our studies indicate that c-Myc has a context-dependent role in mediating the function of Apc in hematopoiesis.
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Registered trials
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.