ArticleExperimental hematology2007
Signals emanating from the membrane proximal region of the thrombopoietin receptor (mpl) support hematopoietic stem cell self-renewal.
Article in Experimental hematology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.Leukemia · 2024Article
- Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome.Stem cell research & therapy · 2024Article
- Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome.Research square · 2024Article
- The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation.Scientific reports · 2018Article
- Dissection of Signaling Events Downstream of the c-Mpl Receptor in Murine Hematopoietic Stem Cells Via Motif-Engineered Chimeric Receptors.Stem cell reviews and reports · 2018Article
- Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.The Journal of experimental medicine · 2017Article
- Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes.The Journal of clinical investigation · 2017Article
- Thrombopoietin induces production of nucleated thrombocytes from liver cells in Xenopus laevis.Scientific reports · 2015Article
- Article
- Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis.Nature medicine · 2013Article
- Lnk deficiency partially mitigates hematopoietic stem cell aging.Aging cell · 2012Article
- Signaling profiling at the single-cell level identifies a distinct signaling signature in murine hematopoietic stem cells.Stem cells (Dayton, Ohio) · 2012Article
- 14-3-3 regulates the LNK/JAK2 pathway in mouse hematopoietic stem and progenitor cells.The Journal of clinical investigation · 2012Article
- Novel hematopoietic progenitor populations revealed by direct assessment of GATA1 protein expression and cMPL signaling events.Stem cells (Dayton, Ohio) · 2011Article
- Thrombopoietin and hematopoietic stem cells.Cell cycle (Georgetown, Tex.) · 2011Review
- Effects of clinically relevant MPL mutations in the transmembrane domain revealed at the atomic level through computational modeling.PloS one · 2011Article
- NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development.The EMBO journal · 2010Article
- Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells.Immunity · 2009Article
- Article
- Miscreant myeloproliferative disorder stem cells.Leukemia · 2008Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveStudies using thrombopoietin -/- (TPO(-/-)) or TPO receptor, mpl(-/-) mice have established a critical role for TPO/mpl signaling in hematopoietic stem cell (HSC) development. In this study, we further dissected mpl signaling in both megakaryopoiesis and HSC function, using mice bearing a truncated mpl receptor lacking the distal 60 amino acids (Delta60). This deletion removes three major signaling tyrosines on the mpl cytoplasmic domain, but retains the membrane proximal Box1 and Box2 domains required for JAK2 activation. MATERIALS AND
methodsCompetitive bone marrow transplantations (BMT) and serial BMTs were performed to study HSC function. Western blot analysis was used to study TPO-stimulated signaling pathways. BM cell cultures in the presence of TPO were used to study megakaryocyte development.
resultsIn agreement with prior findings, we show that Delta60 BM cells cultured in TPO generated normal numbers of megakaryocytes, but with greatly reduced ploidy. As expected from the deletion of three signaling tyrosine residues, freshly isolated Delta60 megakaryocytes showed marked reduction in all known TPO-stimulated signaling pathways tested, including signal transducers and activators of transcription (Stat) 5, Stat3, Akt, and p42/44 mitogen-activated kinase. We found that Delta60 mice displayed normal short-term (ST-HSC) activities and marginally compromised long-term (LT-HSC) stem cell activities in primary transplantation. In addition, Delta60 mice supported HSC self-renewal for at least two serial BMTs.
conclusionOur data reveal a pivotal role for an unknown signal emanating from the membrane proximal region of the mpl receptor or from JAK2 itself in maintaining stem cell activity and self-renewal, in addition to its role in megakaryocytopoiesis and thrombopoiesis.
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