Clarification of whole scheme of developmental pathway in hematopiesis by fate mapping using a genetic marking system

使用遗传标记系统通过命运图谱阐明造血发育途径的整个方案

• 批准号: 21390297
• 负责人: KAWAMOTO Hiroshi
• 金额: $ 11.4万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390297/
• 关键词: 造血; 前駆細胞; 系列決定; T細胞; ミエロイド系細胞; 細胞分化; T前駆細胞; Notchシグナル; フェイトマッピング; Bcl11b; Bclllb; B前駆細胞

We have previously proposed a model of hematopoiesis in which myeloid potential is retained along with development towards T, B and erythroid lineages. In this research project, we aimed to validate this model. Validation of myeloid-B progenitors in fetal hematopoiesis by a single cell analysis was completed(to be submitted). Validation of myeloid-T progenitor stage was achieved by fixing myeloid-T progenitors using a developmental arrest-inducing culture system(Ikawa et al, Science, 2010). Fate map approaches using genetic marking mouse have not yet completed, but a useful line(Flt3-ER-Cre mouse) has been successfully made, and preliminary experiment has provided some promising data. Collectively, the project has been very successful.

我们之前提出了一种造血模型，其中髓系潜能随着向 T、B 和红系谱系的发育而保留。在这个研究项目中，我们的目的是验证这个模型。通过单细胞分析对胎儿造血中的骨髓-B 祖细胞的验证已完成（待提交）。通过使用发育停滞诱导培养系统固定骨髓-T祖细胞来实现骨髓-T祖细胞阶段的验证(Ikawa等人，Science，2010)。使用基因标记小鼠的命运图谱方法尚未完成，但一个有用的品系（Flt3-ER-Cre小鼠）已成功制备，初步实验提供了一些有希望的数据。总的来说，该项目非常成功。

项目成果

Notch activation in thymic epithelial cells induces development of thymic microenvironments

• DOI: 10.1016/j.molimm.2009.01.015
• 发表时间: 2009-05-01
• 期刊: MOLECULAR IMMUNOLOGY
• 影响因子: 3.6
• 作者: Masuda, Kyoko;Germeraad, Wilfred T. V.;Kawamoto, Hiroshi
• 通讯作者: Kawamoto, Hiroshi

Induction of self-renewal program in developing hematopoietic progenitors by inhibiting their differentiation

通过抑制造血祖细胞的分化来诱导其自我更新程序

• 发表时间: 2009
• 作者: Watarai;H.;Kubo;M.;Taniguchi;M.;河本宏
• 通讯作者: 河本宏

In vitro human G-CSF mobilized CD34+derived T-cell progenitors fully mature in vivo

体外人 G-CSF 动员 CD34 衍生的 T 细胞祖细胞在体内完全成熟

• 发表时间: 2010
• 期刊: Blood
• 影响因子: 20.3
• 作者: Meek B;Cloosen S;Borsotti C;Elssen J V;Vanderlocht J;Schnijderberg M;Poel M van der;Leewis B;Hesselink R;Manz M G;Katsura Y;Kawamoto H;Germeraad W TV;and Bos G MJ
• 通讯作者: and Bos G MJ

Poised lineage specification in multipotent hematopoietic progenitor cells by the polycomb protein Bmi1.

通过多梳蛋白 Bmi1 确定多能造血祖细胞的谱系规范。

• 发表时间: 2010
• 期刊: Cell Stem Cell
• 影响因子: 23.9
• 作者: Oguro H;Y Jin;H Ichikawa;T Ikawa;S Yamazaki;H Kawamoto;H Nakauchi;A Iwama
• 通讯作者: A Iwama

Retention and termination of myeloid potential in T cell progenitors

T 细胞祖细胞中骨髓潜能的保留和终止

• 发表时间: 2009
• 作者: Tashiro T;Izumikawa K;Tashiro M;Morinaga Y;Nakamura S;Imamura Y;Miyazaki T;Kakeya H;Yamamoto Y;Yanagihara K;Hayashi T;Nagayasu T;Kohno S;河本宏
• 通讯作者: 河本宏