ArticleNature2014
The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis.Investigational new drugs · 2023Pooled it
- Selpercatinib mitigates microglia-mediated neuroinflammation by inhibiting RET signaling and NLRP3 inflammasome activation.Frontiers in immunology · 2026Article
- Neuroepithelial VIP-VIPR1 interactions differentially control enteric type 1 and type 2 immunity.Nature immunology · 2025Article
- GDF15 regulates development and growth of sympathetic neurons to enhance energy expenditure and thermogenesis.Experimental & molecular medicine · 2025Article
- Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives.Cell communication and signaling : CCS · 2024Review
- Review
- Exploring extramedullary hematopoiesis: unraveling the hematopoietic microenvironments.Frontiers in hematology · 2024Article
- Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.Biochemical pharmacology · 2023Review
- Selective RET inhibitors shift the treatment pattern of RET fusion-positive NSCLC and improve survival outcomes.Journal of cancer research and clinical oncology · 2023Article
- GDNF family receptor alpha-like antagonist antibody alleviates chemotherapy-induced cachexia in melanoma-bearing mice.Journal of cachexia, sarcopenia and muscle · 2023Article
- Amyloid-mediated remineralization for tooth hypoplasia of cleidocranial dysplasia.Frontiers in cellular and infection microbiology · 2023Article
- Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance.Frontiers in endocrinology · 2023Review
- The monoculture of cord-blood-derived CD34Stem cell reports · 2022Article
- Cerebrolysin induces hair repigmentation associated to MART-1/Melan-A reactivation.European journal of medical research · 2022Article
- Article
- Neuroimmune Interactions in Peripheral Organs.Annual review of neuroscience · 2022Review
- Development and clinical advancement of small molecules forActa pharmaceutica Sinica. B · 2022Review
- Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.Nature communications · 2022Article
- Heterogeneity of ILC2s in the Intestine; Homeostasis and Pathology.Frontiers in immunology · 2022Review
- RET kinase inhibitors forTherapeutic advances in medical oncology · 2022Review
1 more citing papers are in PubMed but not listed here.
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 3 institutions in 3 countries.
Funding
Abstract
Haematopoiesis is a developmental cascade that generates all blood cell lineages in health and disease. This process relies on quiescent haematopoietic stem cells capable of differentiating, self renewing and expanding upon physiological demand. However, the mechanisms that regulate haematopoietic stem cell homeostasis and function remain largely unknown. Here we show that the neurotrophic factor receptor RET (rearranged during transfection) drives haematopoietic stem cell survival, expansion and function. We find that haematopoietic stem cells express RET and that its neurotrophic factor partners are produced in the haematopoietic stem cell environment. Ablation of Ret leads to impaired survival and reduced numbers of haematopoietic stem cells with normal differentiation potential, but loss of cell-autonomous stress response and reconstitution potential. Strikingly, RET signals provide haematopoietic stem cells with critical Bcl2 and Bcl2l1 surviving cues, downstream of p38 mitogen-activated protein (MAP) kinase and cyclic-AMP-response element binding protein (CREB) activation. Accordingly, enforced expression of RET downstream targets, Bcl2 or Bcl2l1, is sufficient to restore the activity of Ret null progenitors in vivo. Activation of RET results in improved haematopoietic stem cell survival, expansion and in vivo transplantation efficiency. Remarkably, human cord-blood progenitor expansion and transplantation is also improved by neurotrophic factors, opening the way for exploration of RET agonists in human haematopoietic stem cell transplantation. Our work shows that neurotrophic factors are novel components of the haematopoietic stem cell microenvironment, revealing that haematopoietic stem cells and neurons are regulated by similar signals.
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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.