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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)浆细胞从脾脏迁移到骨髓的机制。为了明确浆细胞迁移到骨髓的机制，对调节分子进行了评估。在引发时注射针对 Flt3 (A2F10) 的拮抗抗体会减少骨髓中的浆细胞数量，并增加脾脏中的浆细胞数量。抗原引发降低了对照小鼠浆细胞上 CXCL12 的表达，但在 A2F10 处理的小鼠中却没有。通过浆细胞上的 Flt3 发出的信号会减少 CXCL12，从而加速浆细胞向骨髓的迁移。这些结果表明，F1t3 信号传导对 CXCL12 表达的调节控制了骨髓中浆细胞的数量。（稿件准备中）2）Wnt/β-catenin信号通路对多能造血细胞的功能。研究Wnt/β-catenin信号通路中与干细胞自我更新有关的一个组成部分。逆转录病毒介导将稳定的β-连环蛋白引入原始小鼠骨髓细胞中，允许在存在基质细胞和细胞因子。这些发现表明经典 Wnt 通路信号传导对多能祖细胞的调节。 (J.Immunol, 2006, 177: 2294-2303)3) 牙齿发育中多能细胞的表征。为了评估牙齿间充质细胞在牙齿发育中的潜力，我们从 E13.5 牙胚细胞中制备了间充质细胞，并评估了它们在培养物中分化的潜力。它们分化成成牙本质细胞、软骨细胞样细胞和成骨细胞样细胞。通过使用 P0-Cre/Rosa26R 小鼠将 NC 衍生细胞追踪为 LacZ^+ 细胞，证实了它们的来源。这些结果表明，发育中的牙齿中存在具有分化为软骨细胞样和成骨细胞样细胞潜力的NC衍生细胞，这些细胞可能有助于牙齿器官发生。 (干细胞, 2007, 25: 78-87) 少