Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE.

Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE.
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通过 RAGE 鉴定负责细胞因子诱导的红细胞和骨髓细胞分化以及造血干细胞转换的关键基因。

DOI:
10.1038/sj.cr.7310115
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发表时间:
2006
期刊:
影响因子:
44.1
通讯作者:
Rodgers,GriffinP
Rodgers,GriffinP
中科院分区:
生物学1区
文献类型:
--
作者:
Chen,Ling;Zhang,Hong;Shi,Ying;Chin,KyungL;Tang,DeliaC;Rodgers,GriffinP

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我们利用一个独特的培养系统来分析基因,蛋白质和细胞表面抗原的表达模式,以及相关基因在红系和髓系分化中的生物学过程,以及造血干细胞(HSCs)响应细胞因子改变的转换。从五个群体的精氨酸刺激的HSC中鉴定的基因特异性片段(266)被分为三组:(1)在单个细胞群体中特异性表达;(2)在两个细胞群体中表达,以及(3)在三个或更多个群体中表达。在145个确定的cDNA中,有3个(2%)是新基因。蛋白质双向凝胶电泳和流式细胞仪分析显示重叠和区分蛋白质表达谱的细胞群研究。在红系和髓系中表达的mRNA的生物学过程映射表明,两个谱系共享的mRNA参与“核心过程”,而在任一谱系中特异性表达的基因与特定过程或细胞成熟相关。本研究的数据支持这一假设,即在红系培养条件下,当用粒细胞集落刺激因子(G-CSF)替代促红细胞生成素(EPO)时,或在骨髓培养环境中,当用EPO替代G-CSF时,定向的HSC(E14或G14)细胞仍然可以被重定向发育为髓系或红系细胞。我们的研究结果表明,在红系和髓系共表达的基因或蛋白质可能是必要的造血谱系的维持和转换。
We utilized a unique culture system to analyze the expression patterns of gene, protein, and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoietic stem cells (HSCs) in response to cytokine alterations. Gene-specific fragments (266) identified from five populations of cytokine-stimulated HSCs were categorized into three groups:(1) expressed specifically in a single cell population;(2) expressed in two cell populations, and (3) expressed in three or more populations. Of 145 defined cDNAs, three (2%) were novel genes. Protein two-dimensional gel electrophoresis and flow cytometry analyses showed overlapped and distinguished protein expression profiles in the cell populations studied. Biological process mapping of mRNAs expressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended'core processes,'whereas genes specifically expressed in either lineage alone were related to specific processes or cellular maturation. Data from this study support the hypothesis that committed HSCs (E14 or G14) cells can still be redirected to develop into myeloid or erythroid cells when erythropoietin (EPO) is replaced with granulocyte-colony stimulating factor (G-CSF) under erythroid-cultured condition or G-CSF with EPO in myeloid-cultured environment, respectively. Our results suggest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenance and switching in hematopoiesis.
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