The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver.
The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver.
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基本的螺旋环螺旋转录因子，心脏和神经rest衍生物表达转录本2，标记斑马鱼中的肝星状细胞：分析星状细胞进入发育中的肝脏。
DOI：
10.1002/hep.25757
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发表时间：
2012-11
期刊：
影响因子：
13.5
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
--
作者：
Yin, Chunyue;Evason, Kimberley J.;Maher, Jacquelyn J.;Stainier, Didier Y. R.
肝星状细胞（HSC）是肝脏特异性间充质细胞，在肝脏发育和损伤中发挥着重要作用。由于缺乏体内数据，我们对 HSC 生物学的了解受到限制。 HSC 和正窦内皮细胞 (SEC) 距离很近，这两种细胞类型之间的相互作用对于它们的发育和功能可能至关重要。在这里，我们介绍了一种标记 HSC 的转基因斑马鱼系 Tg(hand2:EGFP)。我们发现斑马鱼 HSC 与其哺乳动物对应物有许多相似之处，包括形态、位置、脂质储存、基因表达谱以及响应急性肝损伤而增加的增殖和基质产生。使用 Tg(hand2:EGFP) 系，我们在发育过程中进行了时间过程分析，揭示了 HSC 在 SEC 之后侵入肝脏。然而，在缺乏大多数内皮细胞（包括 SEC）的突变体中，HSC 仍然进入肝脏，这表明 SEC 不是 HSC 分化或进入肝脏所必需的。在缺乏 SEC 的情况下，HSC 与肝胆细胞异常相关，表明 SEC 在肝脏发育过程中影响 HSC 定位。我们分析了调节 HSC 发育的因素，结果表明抑制血管内皮生长因子信号传导可显着减少进入肝脏的 HSC 数量。我们还进行了试点化学筛选，并确定了两种在开发过程中影响 HSC 数量的化合物。我们的工作首次全面描述了斑马鱼 HSC 的发育，并揭示了 SEC 在 HSC 本地化中的要求。 Tg(hand2:EGFP) 系列代表了 HSC 行为体内分析和分子解剖的独特工具。
Hepatic stellate cells (HSCs) are liver-specific mesenchymal cells that play vital roles in liver development and injury. Our knowledge of HSC biology is limited by the paucity of in vivo data. HSCs and sinusoidal endothelial cells (SECs) reside in close proximity and interactions between these two cell types are potentially critical for their development and function. Here we introduce a transgenic zebrafish line, Tg(hand2:EGFP), that labels HSCs. We find that zebrafish HSCs share many similarities with their mammalian counterparts, including morphology, location, lipid storage, gene expression profile, and increased proliferation and matrix production in response to an acute hepatic insult. Using the Tg(hand2:EGFP) line, we conducted time course analyses during development to reveal that HSCs invade the liver after SECs do. However, HSCs still enter the liver in mutants that lack most endothelial cells including SECs, indicating that SECs are not required for HSC differentiation or their entry into the liver. In the absence of SECs, HSCs become abnormally associated with hepatic biliary cells, suggesting that SECs influence HSC localization during liver development. We analyzed factors that regulate HSC development and show that inhibition of vascular endothelial growth factor signaling significantly reduces the number of HSCs that enter the liver. We also performed a pilot chemical screen and identified two compounds that affect HSC numbers during development. Our work provides the first comprehensive description of HSC development in zebrafish and reveals the requirement of SECs in HSC localization. The Tg(hand2:EGFP) line represents a unique tool for in vivo analysis and molecular dissection of HSC behavior.
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影响因子：
9.2
作者：
Habeck, H;Odenthal, J;Schulte-Merker, S
通讯作者：
Schulte-Merker, S
影响因子：
4.2
作者：
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作者：
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Geerts, A
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56.9
作者：
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Zaret, KS
影响因子：
3.5
作者：
Her, GM;Chiang, CC;Wu, JL
通讯作者：
Wu, JL