Zebrafish small molecule screen in reprogramming/cell fate modulation.
Zebrafish small molecule screen in reprogramming/cell fate modulation.
复制标题
斑马鱼小分子筛选重编程/细胞命运调节。
DOI：
10.1007/978-1-60761-691-7_20
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Munson,KathleenM
中科院分区：
文献类型：
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作者：
Yeh,Jing-RueyJ;Munson,KathleenM
长期以来，胚胎斑马鱼一直被用于谱系追踪研究。在斑马鱼胚胎中，细胞命运身份可以通过全贴装原位杂交来确定，或者如果使用荧光报告系，可以通过活体胚胎的可视化来确定。我们使用胚胎斑马鱼来研究白血病致癌基因AML1-ETO对造血细胞命运的调节作用。AML1-ETO的诱导表达能够有效地将造血祖细胞从红系细胞重编程为髓系细胞。利用AML1-ETO的斑马鱼模型，我们进行了化学筛选，以确定在AML1-ETO存在时抑制细胞命运开关的小分子。本文讨论的方法可能广泛适用于识别调节其他细胞命运决定的小分子。
Embryonic zebrafish have long been used for lineage-tracing studies. In zebrafish embryos, the cell fate identities can be determined by whole-mount in situ hybridization, or by visualization of live embryos if using fluorescent reporter lines. We use embryonic zebrafish to study the effects of a leukemic oncogene AML1-ETO on modulating hematopoietic cell fate. Induced expression of AML1-ETO is able to efficiently reprogram hematopoietic progenitor cells from erythroid to myeloid cell fate. Using the zebrafish model of AML1-ETO, we performed a chemical screen to identify small molecules that suppress the cell fate switch in the presence of AML1-ETO. The methods discussed herein may be broadly applicable for identifying small molecules that modulate other cell fate decisions.