Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro

Li, Weiming; Johnson, Scott A.; Shelley, W. Christopher; Ferkowicz, Michael J.; Morrison, Paul R.; Li, Yanjun; Yöder, Mervin C.

doi:10.1182/blood-2003-03-0729

Cited by 54 publications

(42 citation statements)

References 35 publications

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“…Primary endothelial cells isolated from the mouse AGM region 41 and a stromal cell line derived from the murine AGM region 42 can each support the expansion of murine bone marrow HSCs. Given the known endothelial defect in B-raf Ϫ/Ϫ embryos, 19 defective AGM endothelium may explain the impaired definitive hematopoiesis in B-raf Ϫ/Ϫ embryos.…”

Section: Discussionmentioning

confidence: 99%

A critical function for B-Raf at multiple stages of myelopoiesis

Kamata

Kang

Lee

et al. 2005

Blood

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IntroductionCytokines play critical roles during hematopoietic development. 1 Some, such as stem cell factor (SCF), regulate early hematopoiesis through their action on multipotent progenitors. 1 Others, such as erythropoietin (Epo), regulate later stages of hematopoiesis through their effects on specific, lineage-committed cells. 1 Thrombopoietin (Tpo), while first identified as a key cytokine regulator of megakaryocyte-lineage development, 2-5 also plays a vital role in hematopoietic progenitor or stem cell biology. 6,7 Cytokine effects are mediated by the activation of specific intracellular signaling pathways following binding to their cognate receptors.While the intracellular signaling pathways activated by most hematopoietic cytokines have been identified, their biologic significance remains poorly understood. The classic mitogen-activated protein (MAP) kinase (Raf/MEK/extracellular signal-related kinase [ERK]) intracellular pathway can affect cell proliferation, apoptosis, and differentiation in various cell lines and systems, 8,9 yet its role in hematopoiesis remains undefined. Moreover, since the MAP kinase cascade is activated by various cytokines, one would predict that its function is context dependent.As an entry point to the classic MAP kinase pathway, Raf kinases play a key role in controlling the signal flow from activated cytokine receptors by activating MAP kinase/ERK kinase 1/2 (MEK 1/2), which in turn activates ERK 1/2, the pathway's key known effector. 10 There are 3 known vertebrate Raf isoforms, A-Raf, B-Raf, and Raf-1. 11 We recently reported that Raf-1 is not required for establishment of the myeloid progenitor compartment in murine bone marrow, megakaryocytopoiesis, or Tpo-induced ERK phosphorylation. 12 As the Raf/MEK/ERK pathway is activated by a number of cytokines, including Tpo, and our Raf-1 findings raised questions about previously reported roles for Raf-1 in megakaryocytopoiesis, 13 we have extended our genetic approach to better understand the role of other Raf family members in myeloid development, including megakaryocytopoiesis.While Raf-1 is the most studied Raf family member, B-Raf is more widely expressed than originally thought and is possibly the most potent MEK/ERK activator among the Raf isoforms. 11,14 Recent reports suggest an important role for B-Raf in a number of pathologic and physiologic events including melanoma, thyroid, ovarian, and colon cancer 15 ; sensory and motor neuron survival 16 ; and midgestational mouse embryogenesis. [17][18][19] Moreover, the classic MAP kinase cascade is frequently activated in leukemia. This is most often due to Ras activating mutations, 20 but primary B-raf mutations have been identified in acute leukemias and malignant lymphomas. [21][22][23] Despite the important role of Ras activating mutations in hematopoietic pathology, and the recent entry of Raf inhibitors into clinical trails, 24-26 the role of B-Raf in hematopoiesis remains undefined.In this study, we characterized the role of B-Raf in myelopoiesis using B-raf Ϫ/Ϫ emb...

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Section: Discussionmentioning

confidence: 99%

A critical function for B-Raf at multiple stages of myelopoiesis

Kamata

Kang

Lee

et al. 2005

Blood

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“…1 Extensive research has identified several cell types, such as endothelial cells, [2][3][4] fibroblasts, 5 adipocytes, 6,7 and osteoblasts, as important constituents of the HSC niche. The most thoroughly investigated are the osteoblasts, with studies showing that increasing their number is associated with HSC expansion.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo

Lymperi

Ersek

Ferraro

et al. 2011

Blood

123

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“…Murine yolk sac-and intraembryonic paraaortic splanchnopleure-derived endothelial cells promoted significant expansion of adult BM-derived HSC and HPC during 4 to 7 days of in vitro coculture. 11 However, isolation of primary endothelial cells from adult murine organs and coculture with BM-derived hematopoietic cells revealed that brain and heart endothelium significantly increased, lung and liver endothelium maintained, and kidney endothelial cells markedly decreased the number of CFU during a 7-day coculture compared with the freshly isolated BM-derived hematopoietic cells. 12 Hematopoietic stem cell-competitive repopulating activity was maintained in heart and liver endothelial cocultures with BM-derived hematopoietic cells while all HSC activity was lost in BM-derived hematopoietic cells cocultured with primary kidney endothelium even when cocultured in the presence of known hematopoietic growth factors that support HSC and HPC maintenance and differentiation in vitro.…”

Section: Article See P 592mentioning

confidence: 94%

“…Although the authors did not pursue further studies on the mechanisms that cause the renal arteries to be deficient in retention of hematopoietic colonies, these data are consistent with some prior published work. Even though mesenchymal cells derived from a variety of vessels and tissues are largely supportive of hematopoiesis, 10 Li et al 11,12 have reported that primary endothelial cells isolated from various vascular beds in embryonic and adult mice differ in their in vitro support of HSC and HPC. Murine yolk sac-and intraembryonic paraaortic splanchnopleure-derived endothelial cells promoted significant expansion of adult BM-derived HSC and HPC during 4 to 7 days of in vitro coculture.…”

Section: Article See P 592mentioning

confidence: 99%