Anterior Definitive Endoderm from ESCs Reveals a Role for FGF Signaling
Anterior Definitive Endoderm from ESCs Reveals a Role for FGF Signaling
复制标题
DOI：
10.1016/j.stem.2008.07.021
复制
发表时间：
2008-10-09
期刊：
影响因子：
23.9
通讯作者：
Brickman, Joshua M.
中科院分区：
文献类型：
--
作者：
Morrison, Gillian M.;Oikonomopoulou, Ifigenia;Brickman, Joshua M.
利用胚胎干细胞（ESC）分化来产生功能性肝脏或胰腺祖细胞以及作为发育生物学的工具，受到无法在体外分离区域特异性的前定形内胚层（ADE）等同物的限制。为了解决这个问题，我们设计了一种策略，在前内胚层标记物Hex以及定形中内胚层标记物Cxcr4的转录控制下使用荧光报告基因。分离Hex(+)Cxcr4(+)分化的胚胎干细胞产生了一个表达ADE标记物的群体，该群体既可以扩增，又有能力向肝脏和胰腺命运分化。Hex报告基因胚胎干细胞也被用于确定无血清贴壁培养中ADE特化的条件，并揭示了成纤维细胞生长因子（FGF）信号在ADE产生中的意外作用。我们在限定的单层分化中的发现表明，FGF信号是早期前中内胚层分化的重要调节因子，而不仅仅是形态发生运动的介质。
The use of embryonic stem cell (ESC) differentiation to generate functional hepatic or pancreatic progenitors and as a tool for developmental biology is limited by an inability to isolate in vitro equivalents of regionally specified anterior definitive endoderm (ADE). To address this, we devised a strategy using a fluorescent reporter gene under the transcriptional control of the anterior endoderm marker Hex alongside the definitive mesendoderm marker Cxcr4. Isolation of Hex(+)Cxcr4(+) differentiating ESCs yielded a population expressing ADE markers that both can be expanded and is competent to undergo differentiation toward liver and pancreatic fates. Hex reporter ESCs were also used to define conditions for ADE specification in serum-free adherent culture and revealed an unexpected role for FGF signaling in the generation of ADE. Our findings in defined monolayer differentiation suggest FGF signaling is an important regulator of early anterior mesendoderm differentiation rather than merely a mediator of morphogenetic movement.