Hepatic stellate cells do not derive from the neural crest

Hepatic stellate cells do not derive from the neural crest
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DOI:
10.1016/j.jhep.2005.09.023
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发表时间:
2006-06-01
影响因子:
25.7
通讯作者:
Pachnis, V
Pachnis, V
中科院分区:
医学1区
文献类型:
--
作者:
Cassiman, D;Barlow, A;Pachnis, V

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背景/目的:基于肝星状细胞(HSC)表达多种神经/神经内分泌特征以及与自主神经末梢的接触,有人假设其来源于神经嵴。 方法:我们在一种所有神经嵴细胞及其衍生物都表达黄色荧光蛋白(YFP)的转基因小鼠品系中,研究了胚胎发育期间肝脏中HSC的出现情况。比较了这些小鼠的细胞YFP表达与胚胎期第11.5天(E11.5)至成年期结蛋白的表达。 结果:YFP在从神经管分层的神经嵴细胞以及所有已知的神经嵴衍生结构和细胞群中大量表达。特别是,表达YFP的细胞完美地模拟了从耳后区域迁移的神经嵴细胞发育为肠神经系统的时空模式。肾上腺髓质内的细胞也呈YFP阳性。对肝脏的分析表明,从E11.5起,表达结蛋白、呈星状、位于肝窦周的HSC就很明显。然而,从E11.5直至成年期,在发育中的肝脏或HSC中均未检测到YFP表达。 结论:这些发现表明HSC并非来源于神经嵴,因此可能来源于横隔间质、内胚层或肝的间皮包膜。(c)2005欧洲肝脏研究协会。由爱思唯尔出版集团出版。保留所有权利。
Background/Aims: Hepatic stellate cells (HSC) have been hypothesised to derive from the neural crest, based on their expression of multiple neural/neuroendocrine features and their contacts with autonomic nerve endings.Methods: We studied the emergence of HSC in the liver during embryonic development in a transgenic mouse line expressing yellow fluorescent protein (YFP) in all neural crest cells and their derivatives. Cellular YFP expression in these mice was compared with desmin expression between embryonic day (E) 11.5 and adulthood.Results: YFP was abundantly expressed in neural crest cells delaminating from the neural tube and in all known neural crest-derived structures and cell populations. In particular, YFP expressing cells perfectly mimicked the spatial and temporal pattern of enteric nervous system development from neural crest cells migrating from the postotic region. Cells within the adrenal medulla were also YFP positive. Analysis of the liver showed that desmin-expressing, stellate-shaped, perisinusoidally located HSC were evident from E11.5 onwards. However, no detectable YFP expression was seen in the developing liver or in HSC, from E11.5 until adulthood.Conclusions: These findings suggest HSC do not descend from the neural crest, and therefore may derive from the septum transversum mesenchyme, from endoderm or from the mesothelial liver capsule. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.