Analysis of hematopoietic lineage plasticity by using inducible transcription factors

利用诱导转录因子分析造血谱系可塑性

基本信息

  • 批准号:
    14370298
  • 负责人:
  • 金额:
    $ 8.9万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2003
  • 项目状态:
    已结题

项目摘要

In order to investigate the molecular mechanism of differentiation and possible lineage switch or trans-differentiation in various hematopoietic lineages, we generated inducible form of myeloid transcription factors C/EBP α and PU.1 and examined their effect in vitro or in vivo. Full length C/EBP a and PU.1 were fused in frame with ligand binding domain of estrogen receptor (C/EBP α -ER and PU.1-ER) so that they can be activated by 4-hydroxy tamoxifen (4-HT). We subcloned. C/EBP α -ER and PU.1-ER into retrovirus vector, pMX-IRES-GFP and infected virus to BaF3 cells. Interestingly, 4-HT treatment of BaF3/CEBP α -ER, BaF3/PU.1l-ER cells induced growth arrest and apoptosis, indicating that C/EBP α -ER and PU.1-ER are working properly. Next we subcloned Cl EBP α -ER and PU.1-ER in H-2K promoter vector made transgenic mice. We obtained transgene integration in 8 lines for C/ EBP a -ER and 5 lines for PU.1-ER. RT-PCR analysis showed that mRNA is expressed in 5 out of 8 C/EBP α -ER transgenics and only one line expressed C/EBP α -ER protein by western blot. C/EBP α -ER was expressed highly in thymus and spleen, moderately in bone marrow and peripheral blood. Gel-shift assay showed that C/ EBP α -ER protein bound to conserved C/EBP binding sequence in response to 4-HT. With these mice in our hand, we are now planning to investigate how ectopically induced C/ EBP α activity affects differentiation of hematopoietic cells at various developmental stages.
为了研究分化的分子机制以及在各种造血谱系中可能的谱系转换或转分化,我们产生了可诱导形式的髓样转录因子C/EBP α和PU. 1,并在体外或体内检测了它们的作用。将全长C/EBP α和PU. 1与雌激素受体的配体结合域(C/EBP α -ER和PU. 1-ER)进行框内融合,使其能被4-羟基三苯氧胺(4-HT)激活。我们进行了亚克隆。将C/EBP α -ER和PU. 1-ER分别克隆入逆转录病毒载体pMX-IRES-GFP中,感染BaF 3细胞。有趣的是,4-HT处理BaF 3/CEBP α -ER和BaF 3/PU. 1 l-ER细胞可诱导生长停滞和凋亡,表明C/EBP α -ER和PU. 1-ER正常工作。然后将C1-EBP α -ER和PU.1-ER分别亚克隆到H-2K启动子载体中,制备转基因小鼠。我们在8个株系中获得了C/EBPa-ER的转基因整合,在5个株系中获得了PU.1-ER的转基因整合。RT-PCR检测结果显示,8株转基因细胞中有5株表达mRNA,Western blot检测结果显示,只有1株表达C/EBP α -ER蛋白。C/EBP α -ER在胸腺和脾脏中高度表达,在骨髓和外周血中中度表达。凝胶迁移实验表明,C/ EBP α -ER蛋白与保守的C/EBP结合序列结合。有了这些小鼠,我们现在计划研究异位诱导的C/ EBP α活性如何影响造血细胞在不同发育阶段的分化。

项目成果

期刊论文数量(36)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Carpino N.: "Identification, cDNA cloning, and targeted deletion of p70, a novel, ubiquitously expressed SH3 domain-containing protein."Mol.Cell.Biol.. 22. 7491-7500 (2002)
Carpino N.:“p70 的鉴定、cDNA 克隆和靶向删除,p70 是一种新型、普遍表达的含有 SH3 结构域的蛋白质。”Mol.Cell.Biol.. 22. 7491-7500 (2002)
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    0
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Kumagai H.: "Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells."Biochem.Biophys.Res.Commun.. 307. 719-729 (2003)
Kumagai H.:“来自鼠骨髓源性肥大细胞的一对新的免疫球蛋白样受体 LMIR1 和 2 的鉴定和表征。”Biochem.Biophys.Res.Commun.. 307. 719-729 (2003)
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    0
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Truong BT.: "CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia."Blood. 101. 1141-1148 (2003)
Truong BT.:“CCAAT/增强子结合蛋白抑制急性髓性白血病的白血病表型。”血液。
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    0
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Watanabe N., Nakajima H., Suzuki H., Oda A., Matsubara Y., Moroi M., Terauchi Y., Kadowaki T., Suzuki H., Koyasu S., Ikeda Y., Hanada M.: "Functional phenotype of phosphoinositide 3-kinase p85alpha-null platelets characterized by an impaired response to G
渡边 N.、中岛 H.、铃木 H.、小田 A.、松原 Y.、森井 M.、寺内 Y.、门胁 T.、铃木 H.、小安 S.、池田 Y.、花田 M.:“功能性
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    0
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Kitamura T., Koshino Y., Shibata F., Oki T., Nakaiima H., Nosaka T., Kumagai H.: "Retrovirus-mediated gene transfer and expression cloning : powerful tools in functional genomics."Exp.Hematol.. 31. 1007-1014 (2003)
Kitamura T.、Koshino Y.、Shibata F.、Oki T.、Nakaiima H.、Nosaka T.、Kumagai H.:“逆转录病毒介导的基因转移和表达克隆:功能基因组学的强大工具。”Exp.Hematol..
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NAKAJIMA Hideaki其他文献

NAKAJIMA Hideaki的其他文献

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{{ truncateString('NAKAJIMA Hideaki', 18)}}的其他基金

Regulation of leukemic stem cells by mitochondrial dynamics
线粒体动力学对白血病干细胞的调节
  • 批准号:
    20H03714
  • 财政年份:
    2020
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Epigenetic Regulation of hematopoietic stem cells by O-GlcNAc transferase
O-GlcNAc 转移酶对造血干细胞的表观遗传调控
  • 批准号:
    26670469
  • 财政年份:
    2014
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
The basic reaserch for the pathologic symptom to improve the survival rate of transplanted bone marrow stromal cells in the injured spinal cord
针对病理症状提高损伤脊髓移植骨髓基质细胞存活率的基础研究
  • 批准号:
    25462290
  • 财政年份:
    2013
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A role for ATOX1 in 5q- syndrome
ATOX1 在 5q 综合征中的作用
  • 批准号:
    24659467
  • 财政年份:
    2012
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
The effects and mechanism of bone marrow stromal cells for spinalcord injury
骨髓基质细胞对脊髓损伤的作用及机制
  • 批准号:
    23791631
  • 财政年份:
    2011
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
The control of neural-glial spinal cells microenvironment after traumatic injury through transfection of neurotrophic factor
转染神经营养因子对创伤后神经胶质脊髓细胞微环境的调控
  • 批准号:
    21791389
  • 财政年份:
    2009
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
A study on characterization of polar stratospheric clouds(PSC) related to ozone depletion
与臭氧消耗相关的极地平流层云(PSC)特征研究
  • 批准号:
    20244077
  • 财政年份:
    2008
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Regulation of self-renewal of leukemic stem cells by hematopoietic transcription factors
造血转录因子对白血病干细胞自我更新的调控
  • 批准号:
    19390259
  • 财政年份:
    2007
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Differentiation control of endogenous and exogenous neural stem cells using neurotrophic factors in spinal cord injury study
在脊髓损伤研究中利用神经营养因子控制内源性和外源性神经干细胞的分化
  • 批准号:
    19791023
  • 财政年份:
    2007
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Regulation of self-renewal of hematopoietic stem cells by bone marrow stromal cells
骨髓基质细胞对造血干细胞自我更新的调控
  • 批准号:
    16390274
  • 财政年份:
    2004
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

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Examining the role of transcription factor c-maf in regulatory T cell differentiation and function in tumor tolerance and immune evasion
检查转录因子 c-maf 在调节性 T 细胞分化和肿瘤耐受和免疫逃避功能中的作用
  • 批准号:
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转录因子c-MYC在淋巴细胞扩增和干性限制中的作用
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Characterization of the role of the bHLH transcription factor HLH-3 in the differentiation and function of neurons with gender specific roles in the nematode C. elegans
线虫线虫中 bHLH 转录因子 HLH-3 在具有性别特异性作用的神经元的分化和功能中的作用的表征
  • 批准号:
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Isoform-specific adipogenic potential of the C/EBP beta transcription factor
C/EBP β 转录因子的异构体特异性脂肪形成潜力
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    183556
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    2009
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Regulation of differentiation and proliferation of granulocytic precursors by C/EBP transcription factor
C/EBP转录因子对粒细胞前体细胞分化和增殖的调节
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C/EBPE--STUDY OF A NOVEL MYELOID TRANSCRIPTION FACTOR
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    6164050
  • 财政年份:
    1979
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    $ 8.9万
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C/EBPE--STUDY OF A NOVEL MYELOID TRANSCRIPTION FACTOR
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    2470429
  • 财政年份:
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C/EBPE--STUDY OF A NOVEL MYELOID TRANSCRIPTION FACTOR
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    6362516
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    1979
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    $ 8.9万
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C/EBPE--STUDY OF A NOVEL MYELOID TRANSCRIPTION FACTOR
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    2882295
  • 财政年份:
    1979
  • 资助金额:
    $ 8.9万
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C/EBPE--STUDY OF A NOVEL MYELOID TRANSCRIPTION FACTOR
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    6512543
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