Multiple actions of stem cell factor in neural crest cell differentiation in vitro

Multiple actions of stem cell factor in neural crest cell differentiation in vitro
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DOI:
10.1006/dbio.1996.0079
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发表时间:
1996-03-15
影响因子:
2.7
通讯作者:
SieberBlum, M
SieberBlum, M
中科院分区:
生物学3区
文献类型:
--
作者:
LangtimmSedlak, CJ;Schroeder, B;SieberBlum, M

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神经嵴是脊椎动物胚胎的短暂组织,在成体生物体中产生大多数初级感觉神经元和色素细胞以及其他细胞类型和组织。许多神经嵴细胞是多能的,因为它们的后代可以产生一种以上的表型。多能神经嵴细胞衍生的细胞在终末分化的位点的存在表明,来自胚胎环境的位置特异性线索,如生长因子,参与指导其生存,增殖和细胞类型的规范。因此,我们研究了一个相关的生长因子,干细胞因子(SCE),在体外无血清培养基中的集落测定神经嵴细胞发育的影响。SCP显示了三个主要影响。(1)SCE对早期神经嵴细胞(即多能细胞和/或其更成熟的后代)有营养作用。只有在整个培养期间SCF存在时才会发生这种效应,而当除了SCF之外还存在神经营养因子时,则观察不到这种效应。(2)更多的集落含有感觉神经元前体在SCF的存在。这种作用被NGF和神经营养因子-3(NT-3)中和,但不被脑源性神经营养因子(BDNF)中和。(3)SCE和任何测试的神经营养因子(NGF、BDNF、NT-3)的组合对黑素生成细胞是营养的,而SCF单独不可检测地影响黑素生成。这表明,无论是这两种类型的因子所需的黑素营养作用或黑素细胞成为依赖于神经营养因子暴露于SCF后。我们观察到SCE只在培养期的前半段需要,而NGF只在后半段需要,这表明后一种可能性。尽管小鼠突变体W(c-kit缺陷)和Steel(SCP缺陷)中的毛色变化以及其他研究人员的几项体内和体外研究先前已经表明SCF是促黑素的,但它们也表明在黑素生成中需要额外的一种或多种因子。我们的数据表明,SCF影响神经嵴细胞的发展在多个层面和黑素细胞的生存介导的SCP和神经营养因子的组合,而不是SCF单独。(C)出版社:Academic Press,Inc.
The neural crest is a transient tissue of the vertebrate embryo that gives rise to most primary sensory neurons and pigment cells in the adult organism, among other cell types and tissues. Many neural crest cells are pluripotent in the sense that their progeny can generate more than one phenotype. The presence of pluripotent neural crest cell-derived cells at sites of terminal differentiation suggests that location-specific cues from the embryonic environment, such as growth factors, are involved in directing their survival, proliferation, and cell type specification. We have therefore examined the influences of one pertinent growth factor, stem cell factor (SCE), on neural crest cell development by in vitro colony assay in a serum-free culture medium. SCP showed three major effects. (1) SCE is trophic for early neural crest cells, that is, either pluripotent cells and/or their more mature progeny. This effect occurs only if SCF is present throughout the culture period, and it is not observed when a neurotrophin is present in addition to SCF. (2) More colonies contain sensory neuron precursors in the presence of SCF. This effect is neutralized by NGF and neurotrophin-3 (NT-3), but not by brain-derived neurotrophic factor (BDNF). (3) The combination of SCE and any neurotrophin tested (NGF, BDNF, NT-3) is trophic for melanogenic cells, whereas SCF alone does not detectably affect melanogenesis. This suggests either that both types of factor are required for melanotrophic action or that melanogenic cells become dependent on neurotrophins after exposure to SCF. Our observation that SCE is required during the first half of the culture period only, and NGF during the second half only, indicates the latter possibility. Whereas coat color changes in the mouse mutants W (c-kit defect) and Steel (SCP defect) and several in vivo and in vitro studies by other investigators have shown previously that SCF is melanotrophic, they also indicated the requirement of an additional factor, or factors, in melanogenesis. Our data suggest that SCF affects neural crest cell development at multiple levels and that survival of melanogenic cells is mediated by a combination of SCP and a neurotrophin, rather than by SCF alone. (C) 1996 Academic Press, Inc.