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Mechanisms of differentiation and maintenance of hematopoietic cells and their supporting microenvironment

造血细胞分化维持机制及其支持微环境

基本信息

批准号：
17590346
负责人：
HAYASHI Shin-ichi
金额：
$ 2.24万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

1)Mechanisms of the plasma cell migration from spleen to bone marrow.To be clear the mechanisms of migration of plasma cells into bone marrow, the regulatory molecule was assessed. An antagonistic antibody against Flt3 (A2F10) injection at priming reduced the numbers of plasma cells in bone marrow, and increased in spleen. Antigen priming reduced the expression of CXCL12 on plasma cells in control mice, but not in A2F10-treated mice. Signaling via Flt3 on plasma cells reduced CXCL12, resulting in accelerating the migration of plasma cells to bone marrow. These results suggested that the regulation of CXCL12 expression by F1t3 signaling controlled plasma cell numbers in bone marrow. (Manuscript in preparation)2)Function of Wnt/β-catenin signaling for multipotent hematopoietic cells.To investigate one component of the Wnt/β-catenin signaling pathway that has been implicated in stem cell self-renewal. Retroviral-mediated introduction of stable β-catenin to primitive murine bone marrow cel … More ls allowed the expansion of multipotential c-Kit^<low>Sca-1^<low/->CD19^-CD11b^-Flt3^-CD43^+AA4.1^+NK1.1^-CD3^- CD11c^-Gr-1^-CD45R^+ cells in the presence of stromal cells and cytokines. These findings implicated the canonical Wnt pathway signaling in regulation of multipotent progenitors. (J. Immunol, 2006, 177: 2294-2303)3)Characterization of multipotent cells in developing teeth.To assess the potential of dental mesenchymal cells in developing teeth, we prepared mesenchymal cells from E13.5 tooth germ cells and assessed their potential for differentiation in culture. They differentiated into odontoblasts, chondrocyte-like cells, and osteoblast-like cells. Their derivation was confirmed by tracing NC-derived cells as LacZ^+ cells using P0-Cre/Rosa26R mice. These results suggest that NC-derived cells with the potential to differentiate into chondrocyte-like and osteoblast-like cells are present in the developing tooth, and these cells may contribute to tooth organogenesis. (Stem Cells, 2007, 25 : 78-87) Less

1)浆细胞从脾脏向骨髓迁移的机制为了明确浆细胞向骨髓迁移的机制，对浆细胞向骨髓迁移的调控分子进行了研究。在引发时注射针对Flt 3的拮抗性抗体（A2 F10）减少骨髓中的浆细胞的数量，并且增加脾脏中的浆细胞的数量。抗原引发降低了对照小鼠浆细胞上CXCL 12的表达，但在A2 F10处理的小鼠中没有。通过浆细胞上的Flt 3的信号传导减少了CXCL 12，导致加速浆细胞向骨髓的迁移。这些结果表明，通过F1 t3信号调节CXCL 12表达控制骨髓中的浆细胞数量。2）Wnt/β-catenin信号通路在多能造血细胞中的功能研究Wnt/β-catenin信号通路中与干细胞自我更新有关的一个组分。逆转录病毒介导稳定β-catenin基因转染小鼠骨髓原代细胞 ...更多信息在<low>基质细胞和细胞因子存在的情况下，ls允许多潜能c-Kit^ Sca-1^<low/-> CD 19 ^-CD 11b ^-Flt 3 ^-CD 43 ^+ AA 4.1 ^+ NK 1.1 ^-CD 3 ^-CD 11 c ^-Gr-1^-CD 45 R ^+细胞扩增。这些发现暗示了多能祖细胞调节中的经典Wnt通路信号传导。(J. Immunol，2006，177：2294-2303）3）发育中牙齿中多能细胞的表征为了评估牙齿间充质细胞在发育中牙齿中的潜力，我们从E13.5牙胚细胞制备间充质细胞，并评估它们在培养物中的分化潜力。它们分化成牙本质细胞、软骨细胞样细胞和成骨细胞样细胞。通过使用P0-Cre/Rosa 26 R小鼠追踪NC衍生的细胞作为LacZ^+细胞来证实它们的来源。这些结果表明，NC衍生的细胞与分化成软骨细胞样和成骨细胞样细胞的潜力存在于发育中的牙齿，这些细胞可能有助于牙齿器官的形成。(Stem Cells，2007，25：78-87）减