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
基本信息
- 批准号:16390274
- 负责人:
- 金额:$ 9.09万
- 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:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In order to analyze m Kirre function in vivo, we set out to disrupt m Kirre in mouse genome. We screened BAC library to obtain genomic fragment containing m Kirre gene and isolated several genomic fragments. Restriction mapping of m Kirre genomic fragment combined with the computer data base search completed the genomic map of m Kirre locus. Targeting vector was designed to replace the first exon and large portion of the 5-promoter region with Neomycin cassette to disrupt m Kirre gene. Completed targeting vector was electroporated into E14 embryonic stem (ES) cells, and approximately 400 Neomycin-resistant clones were selected and processed to identify homologously recombinant clones by Southern hybridization. We obtained one correctly targeted clone, which was confirmed by hybridizing with 5'- and 3-probes, together with Neo-probe. We are currently making chimeric mice by injecting this clone into blastcysts from C57BL/6 mice.As for ISF, we performed cDNA microarray analysis of bone marrow stromal cell lines overexpressing ISF and ShIF. Comparing expression profiles of MS10 cells expressing ISF, ShIF or mock plasmids revealed that TIMP-3 and SFRP-1 were down-regulated by ISF overexpression. By re-expressing TIMP-3 or SFRP-1 genes in MS10/ ISF cells, the enhanced hematopoietic stem cell (HSC) supporting activity of MS10/ ISF cells reduced a level similar to that of parental MS10 cells. These results indicate that TIMP-3 and SFRP-1 play critical roles in enhanced HSC activity conferred by ISF.
为了分析m Kirre在体内的功能,我们着手干扰小鼠基因组中的m Kirre。对BAC文库进行筛选,获得含有m-Kirre基因的基因组片段,并分离出多个基因组片段。M-Kirre基因片段限制性内切酶图谱与计算机数据库检索相结合,完成了m-Kirre基因座的基因组图谱。设计靶向载体,用新霉素盒取代第一外显子和5-启动子的大部分区域,干扰m-KirRE基因。将已完成的靶向载体电击入E14胚胎干细胞,筛选出约400个新霉素抗性克隆,经Southern杂交鉴定同源重组克隆。我们获得了一个正确的靶向克隆,通过与5‘-和3-探针以及Neo-探针的杂交得到了证实。我们目前正在通过将该克隆注射到C57BL/6小鼠的囊胚中来制造嵌合小鼠。至于ISF,我们对高表达ISF和ShIF的骨髓基质细胞系进行了基因芯片分析。比较表达ISF、SHIF和模拟质粒的MS10细胞的表达谱,发现ISF过表达下调了TIMP-3和SFRP-1。通过在MS10/ISF细胞中重新表达TIMP-3或SFRP-1基因,MS10/ISF细胞增强的造血干细胞(HSC)支持活性降低到与亲代MS10细胞相似的水平。这些结果表明TIMP-3和SFRP-1在ISF增强HSC活性中起关键作用。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Integrin αIIbβ3 induces the adhesion and activation of mast cells through interaction with fibrinogen
整合素αIIbβ3通过与纤维蛋白原相互作用诱导肥大细胞粘附和活化
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Baba T;Mimura J;Nakamura N;Harada N;Yamamoto M;Morohashi K;Fujii-Kuriyama Y.;沖 俊彦;中島 秀明;中島 秀明;福地 由美;川島 敏行;沖俊彦
- 通讯作者:沖俊彦
Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple-lineage leukemogenesis
- DOI:10.1172/jci200522725
- 发表时间:2005-04-01
- 期刊:
- 影响因子:15.9
- 作者:Ono, R;Nakajima, H;Nosaka, T
- 通讯作者:Nosaka, T
Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells
- DOI:10.1016/j.bbrc.2005.11.146
- 发表时间:2006-02-03
- 期刊:
- 影响因子:3.1
- 作者:Nakajima, H;Shibata, F;Kitamura, T
- 通讯作者:Kitamura, T
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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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 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:
$ 9.09万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
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
- 批准号:
14370298 - 财政年份:2002
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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