Domain-specific biological functions of the transcription factor Gata2 on hematopoietic differentiation of mouse embryonic stem cells
Domain-specific biological functions of the transcription factor Gata2 on hematopoietic differentiation of mouse embryonic stem cells
复制标题
转录因子Gata2对小鼠胚胎干细胞造血分化的域特异性生物学功能
DOI：
10.1111/gtc.12628
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发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Hara Takahiko
中科院分区：
文献类型：
--
作者：
Kitajima Kenji;Kanokoda Mai;Nakajima Marino;Hara Takahiko
从发育胚胎的主动脉/性腺/中肾区域的生血内皮细胞（HEC）产生小鼠造血干细胞需要锌指转录因子Gata 2。在先前的研究中，Gata 2在体外的强制表达促进了从小鼠胚胎干细胞（ESC）分化的中胚层细胞的HEC的产生。我们的研究小组先前已经证明，Gata 2在ESC衍生的HEC中的强制表达增强了红细胞和巨核细胞的分化，并抑制了巨噬细胞的分化。然而，Gata 2的多种功能的调节方式仍不清楚。当与OP 9基质细胞（OP 9系统）共培养时，小鼠ESC分化为各种类型的造血细胞。使用该系统和诱导型基因盒交换系统，该系统有助于在相同的基因表达调控单元下建立携带诱导型转基因的ESC，在本研究中系统地剖析了Gata 2的结构域特异性功能。我们确定Gata 2的N末端（氨基酸1-110）区域是红细胞诱导区域，中间（氨基酸111-200）和C末端（氨基酸413-480）区域都是巨核细胞诱导区域。此外，目前的数据强烈表明，这些区域中的每一个之间的分子内拮抗相互作用微调Gata 2的生物学功能。
The generation of mouse hematopoietic stem cells from hemogenic endothelial cells (HECs) in the aorta/gonad/mesonephros region of developing embryos requires a zinc finger transcription factorGata2. In the previous study, an enforced expression ofGata2in vitro promoted the production of HECs from mesodermal cells differentiated from mouse embryonic stem cells (ESCs). Our research group has previously demonstrated that the enforced expression ofGata2in ESC‐derived HECs enhances erythroid and megakaryocyte differentiation and inhibits macrophage differentiation. However, the manner in which the multiple functions of Gata2 are regulated remains unclear. Mouse ESCs differentiate into various types of hematopoietic cells when cocultured with OP9 stromal cells (OP9 system). Using this system and the inducible gene cassette exchange system, which facilitates the establishment of ESCs carrying inducible transgenes under an identical gene expression regulatory unit, the domain‐specific functions of Gata2 were systematically dissected in this study. We determined that the N‐terminal (amino acid 1–110) region of Gata2 was an erythroid‐inducing region, both the middle (amino acid 111–200) and C‐terminal (amino acid 413–480) regions were megakaryocyte‐inducing regions. Furthermore, the present data strongly suggest that intramolecular antagonistic interactions between each of these regions fine‐tune the biological functions of Gata2.