دورية أكاديمية
أعرض في EDS

The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function.

التفاصيل البيبلوغرافية
العنوان: The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function.
المؤلفون: Fonseca-Pereira D; 1] Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal [2]., Arroz-Madeira S; 1] Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal [2]., Rodrigues-Campos M; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal., Barbosa IA; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal., Domingues RG; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal., Bento T; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal., Almeida AR; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal., Ribeiro H; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal., Potocnik AJ; 1] Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK [2] Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK., Enomoto H; 1] Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Graduate School of Medicine, Kobe University7-5-1 Kusunoki-cho, Chuo-ku, Kobe City, Hyogo 650-0017, Japan., Veiga-Fernandes H; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
المصدر: Nature [Nature] 2014 Oct 02; Vol. 514 (7520), pp. 98-101. Date of Electronic Publication: 2014 Jul 27.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Hematopoietic Stem Cells/*cytology , Hematopoietic Stem Cells/*metabolism , Nerve Growth Factors/*metabolism , Proto-Oncogene Proteins c-ret/*metabolism, Animals ; Cell Survival ; Cyclic AMP Response Element-Binding Protein/metabolism ; Enzyme Activation ; Female ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-ret/deficiency ; Proto-Oncogene Proteins c-ret/genetics ; Signal Transduction ; Stem Cell Niche ; bcl-X Protein/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
مستخلص: 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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معلومات مُعتمدة: MC_U117565359 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (BCL2L1 protein, human)
0 (Bcl2l1 protein, mouse)
0 (Cyclic AMP Response Element-Binding Protein)
0 (Nerve Growth Factors)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (bcl-X Protein)
EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
EC 2.7.10.1 (RET protein, human)
EC 2.7.10.1 (Ret protein, mouse)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
تواريخ الأحداث: Date Created: 20140801 Date Completed: 20141023 Latest Revision: 20220129
رمز التحديث: 20231215
DOI: 10.1038/nature13498
PMID: 25079320
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/nature13498