Dual role of Mpl receptor during the establishment of definitive hematopoiesis

Petit, Laurence; Volle-Challier, Cécile; Fleury, Maud; Péault, Bruno; Souyri, Michèle

doi:10.1242/dev.001818

Cited by 54 publications

(56 citation statements)

References 49 publications

(38 reference statements)

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“…But so far, very few extrinsic factors have been shown to be involved in the emergence, proliferation and survival of AGM HSCs. Mpl mRNA (which codes for the Tpo receptor) is found in the AGM hematopoietic clusters as tested by in situ hybridization (Petit-Cocault et al, 2007). Interestingly, AGM HSCs from Mpl -/-embryos have normal long-term repopulating potential but show a defect in the self renewal capacity.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown to negatively modulate the development of hematopoiesis by stimulating the differentiation of PCLP + CD45 -cells to endothelial cells in the AGM region. Recently, the Thrombopoietin/Mpl signaling pathway has been shown to play a role in the regulation of HSCs in the mouse embryo (Petit-Cocault et al, 2007). Nevertheless, so far very few studies have clearly demonstrated an in vivo role of adult cytokines in embryonic HSC regulation.…”

Section: Growth Factors and Embryonic Hscsmentioning

confidence: 99%

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The roles of BMP and IL-3 signaling pathways in the control of hematopoietic stem cells in the mouse embryo

Robin¹,

Durand²

2010

Int. J. Dev. Biol.

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During mouse ontogeny, the first adult-type hematopoietic stem cells (HSC) are autonomously generated at mid-gestation in the AGM (Aorta-Gonad-Mesonephros) region. Successively present in different anatomical sites where they will expand, HSCs will finally colonize the bone marrow (BM) where they will reside during the entire adult life. In the bone marrow, both HSC self-renewal and differentiation are controlled at cellular and molecular levels by interactions with the stromal microenvironment. So far, very little is known about the extracellular factors involved in the regulation of embryonic HSC emergence, survival and expansion. In the present review, we outline the BMP and IL-3 signaling pathways that are critical for the growth and potential of embryonic HSCs. We will also discuss how these pathways might be integrated with the ones of Notch and Mpl/thrombopoietin, also identified as important key regulators of AGM HSC activity.

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Section: Discussionmentioning

confidence: 99%

Section: Growth Factors and Embryonic Hscsmentioning

confidence: 99%

The roles of BMP and IL-3 signaling pathways in the control of hematopoietic stem cells in the mouse embryo

Robin¹,

Durand²

2010

Int. J. Dev. Biol.

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“…5,15 However, Mpl mRNA expression can be detected in the AGM, fetal liver and yolk sac as early as E10.5, 34 …”

Section: Stem Cell Role For Tpomentioning

confidence: 99%

Thrombopoietin and hematopoietic stem cells

Graaf

Metcalf²

2011

Cell Cycle

128

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“…51,52 Subsequent studies of this model have demonstrated the role of TPO-MPL signalling in the regulation of HSCs in adult mice 53 and in the establishment of definitive hematopoiesis during embryonic development. 54,55 On the other hand, the presence of residual functional platelets in MPL-deficient animals point to the existence of other factors involved in platelet formation, and these mice have proved an extremely useful model to identify such factors. Various studies have shown that the interleukins IL-3, IL-5, IL-6, IL-11 and IL-17 do not participate in the residual thrombopoiesis.…”

Section: Congenital Amegakaryocytic Thrombocytopenia (Camt)mentioning

confidence: 99%

The contribution of mouse models to the understanding of constitutional thrombocytopenia

et al. 2016

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Article summary• Constitutional thrombocytopenias of hereditary origin have long been poorly studied due to the difficulties of obtaining invasive marrow samples.• Genetic engineering has allowed the generation of numerous mouse models for all these pathologies, providing invaluable information to understanding these diseases and serving as preclinical models to test new therapies.Constitutional thrombocytopenias result from genetic mutations affecting platelet production. These rare diseases are still underdiagnosed, especially in adults, because they remain little-known and have a highly variable expression. Autoimmune thrombocytopenia is still often wrongly diagnosed, thereby leading to the inadequate management of patients, with occasionally inappropriate splenectomy. The diagnosis of congenital thrombocytopenia relies on cytological and functional platelet analyses performed almost exclusively in specialized laboratories. Furthermore, about 50% of thrombocytopenias, associated or not with a thrombopathy, still remain of unknown origin. 1 In cases where platelet studies orient the diagnosis to a known disease, the detection of mutations in the suspected genes can C onstitutional thrombocytopenias result from platelet production abnormalities of hereditary origin. Long misdiagnosed and poorly studied, knowledge about these rare diseases has increased considerably over the last twenty years due to improved technology for the identification of mutations, as well as an improvement in obtaining megakaryocyte culture from patient hematopoietic stem cells. Simultaneously, the manipulation of mouse genes (transgenesis, total or conditional inactivation, introduction of point mutations, random chemical mutagenesis) have helped to generate disease models that have contributed greatly to deciphering patient clinical and laboratory features. Most of the thrombocytopenias for which the mutated genes have been identified now have a murine model counterpart. This review focuses on the contribution that these mouse models have brought to the understanding of hereditary thrombocytopenias with respect to what was known in humans. Animal models have either i) provided novel information on the molecular and cellular pathways that were missing from the patient studies; ii) improved our understanding of the mechanisms of thrombocytopoiesis; iii) been instrumental in structure-function studies of the mutated gene products; and iv) been an invaluable tool as preclinical models to test new drugs or develop gene therapies. At present, the genetic determinants of thrombocytopenia remain unknown in almost half of all cases. Currently available high-speed sequencing techniques will identify new candidate genes, which will in turn allow the generation of murine models to confirm and further study the abnormal phenotype. In a complementary manner, programs of random mutagenesis in mice should also identify new candidate genes involved in thrombocytopenia.The contribution of mouse models to the understanding of constitutional thrombocytope...

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Dual role of Mpl receptor during the establishment of definitive hematopoiesis

Cited by 54 publications

References 49 publications

The roles of BMP and IL-3 signaling pathways in the control of hematopoietic stem cells in the mouse embryo

The roles of BMP and IL-3 signaling pathways in the control of hematopoietic stem cells in the mouse embryo

Thrombopoietin and hematopoietic stem cells

The contribution of mouse models to the understanding of constitutional thrombocytopenia

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