Comparative gene expression analysis of zebrafish and mammals identifies common regulators in hematopoietic stem cells
Comparative gene expression analysis of zebrafish and mammals identifies common regulators in hematopoietic stem cells
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DOI：
10.1182/blood-2009-07-232322
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发表时间：
2010-01-14
期刊：
影响因子：
20.3
通讯作者：
Suda, Toshio
中科院分区：
文献类型：
--
作者：
Kobayashi, Isao;Ono, Hiromasa;Suda, Toshio
硬骨鱼的造血维持在肾脏中。我们以前报道过，Hoechst染料流出活性的造血干细胞（HSC）是高度保守的脊椎动物，Hoechst可以用来纯化HSC硬骨鱼肾脏。与HSC活性密切相关的调节分子在脊椎动物中也可能是保守的。在这项研究中，我们通过比较斑马鱼、小鼠和人类HSC的基因表达谱，确定了HSC中进化上保守的分子组分。斑马鱼肾侧群细胞（zSPs）的基因芯片数据显示，参与细胞连接和信号转导的基因在zSPs中倾向于上调，而参与DNA复制的基因倾向于下调。zSP的这些特性与哺乳动物HSC的特性相似。重叠基因表达分析显示，40个基因在这3种HSC中普遍表达上调。这些基因中的一些，如egr 1，gata 2和id 1，先前已经涉及HSC的调节。斑马鱼肾脏原位杂交显示egr 1，gata 2和id 1的表达结构域与zSP的标记物abcg 2a重叠。这些结果表明，在这项研究中确定的重叠基因在HSC中的调控，并发挥重要作用，在其功能。（血。2010; 115：e1-e9）
Hematopoiesis in teleost fish is maintained in the kidney. We previously reported that Hoechst dye efflux activity of hematopoietic stem cells (HSCs) is highly conserved in vertebrates, and that Hoechst can be used to purify HSCs from teleost kidneys. Regulatory molecules that are strongly associated with HSC activity may also be conserved in vertebrates. In this study, we identified evolutionarily conserved molecular components in HSCs by comparing the gene expression profiles of zebrafish, murine, and human HSCs. Microarray data of zebrafish kidney side population cells (zSPs) showed that genes involved in cell junction and signal transduction tended to be up-regulated in zSPs, whereas genes involved in DNA replication tended to be down-regulated. These properties of zSPs were similar to those of mammalian HSCs. Overlapping gene expression analysis showed that 40 genes were commonly up-regulated in these 3 HSCs. Some of these genes, such as egr1, gata2, and id1, have been previously implicated in the regulation of HSCs. In situ hybridization in zebrafish kidney revealed that expression domains of egr1, gata2, and id1 overlapped with that of abcg2a, a marker for zSPs. These results suggest that the overlapping genes identified in this study are regulated in HSCs and play important roles in their functions. (Blood. 2010; 115: e1-e9)