GFAP Delta as Divergent Marker of Human Glial Progenitors
Cristina Zalfa, C. Grasselli, G. Santilli, D. Ferrari, G. Lamorte, A. Vescovi, L. Filippis
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引用次数: 2
Abstract
Background: Human Neural Stem Cells (hNSCs) are responsible for brain development at prenatal and postnatal stages and for tissue homeostasis and repair after injury on adulthood. The identification of hNSC specific markers is still a debated argument. GFAP-δ, the delta isoform of Glial Fibrillary Acidic Protein (GFAP), is particularly expressed in the Subventricular Zone (SVZ) of the brain and its expression has been related to long-term quiescent NSC. On the other hand, another cytoskeletal protein, gelsolin, is expressed in Neural Progenitor Cells (NPCs) migrating from the SVZ. Methods: In this study, we intended to investigate by immunocytochemistry the co-expression of GFAP-δ and gelsolin in different sources of hNSCs, and hNPCs, with particular emphasis on Good Manifacture Procedures (GMPs) grade hNSC currently used in two clinical trials on Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) patients. Results: We found that the two proteins are co-expressed by undifferentiated GFAP+ cells but tend to localize in different sub-cellular compartments and to segregate in divergent GFAP+ progenies along with differentiation. Interestingly, we proved that, after transplantation into the brain of rodent models of focal demyelination or transient global ischemia, hNSC integrating in the SVZ still retain the co-expression of GFAP-δ and gelsolin, indicating that hNSC intrinsically co-express the two proteins at the stem stage. Conclusion: These findings suggest that GFAP-δ and gelsolin may represent two candidate markers to distinguish NSC from NSC-deriving divergent astroglial phenotypes. GFAP Delta as Divergent Marker of Human Glial Progenitors Cristina Zalfa1, Chiara Grasselli1, Guido Santilli1, Daniela Ferrari1, Giuseppe Lamorte2, Angelo Luigi Vescovi1,2,3 and Lidia De Filippis3* 1Department of Biotechnologies and Biosciences, Universita’ Milano Bicocca, Piazza della Scienza, Milan, Italy 2Istituto C.S.S. Mendel, Viale Regina Margherita, Roma, Italy 3Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy *Corresponding author: Lidia De Filippis, Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG), Italy, Tel: +39(0882)410346; E-mail: lidia.defilippis@unimib.it; l.defilippis@operapadrepio.it Received August 03, 2018; Accepted September 11, 2018; Published September 17, 2018 Citation: Zalfa C, Grasselli C, Santilli G, Ferrari D, Lamorte G, et al. (2018) GFAP Delta as Divergent Marker of Human Glial Progenitors. Stem Cell Res Ther 8: 437. doi: 10.4172/2157-7633.1000437 Copyright: © 2018 Zalfa C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
GFAP δ作为人神经胶质祖细胞分化标记
背景:人神经干细胞(hNSCs)在产前和产后阶段负责大脑发育,并在成年期损伤后负责组织稳态和修复。hNSC特异性标记的鉴定仍然是一个有争议的论点。GFAP-δ是胶质纤维酸性蛋白(GFAP)的δ型异构体,在脑室下区(SVZ)表达,其表达与长期静止的NSC有关。另一方面,另一种细胞骨架蛋白,凝胶蛋白,在从SVZ迁移的神经祖细胞(npc)中表达。方法:在这项研究中,我们打算通过免疫细胞化学研究GFAP-δ和gelsolin在不同来源的hNSCs和hNPCs中的共表达,特别强调目前在肌萎缩性侧索硬化症(ALS)和多发性硬化症(MS)患者的两项临床试验中使用的gmp级hNSC。结果:我们发现这两种蛋白在未分化的GFAP+细胞中共表达,但倾向于定位于不同的亚细胞区室,并在分化的GFAP+后代中分离。有趣的是,我们证明,在移植到局灶性脱髓鞘或短暂性全脑缺血的啮齿动物模型后,整合到SVZ的hNSC仍然保留GFAP-δ和gelsolin的共表达,这表明hNSC在干细胞阶段本质上共表达这两种蛋白。结论:这些发现提示GFAP-δ和gelsolin可能是区分NSC与NSC衍生的不同星形胶质表型的两个候选标记物。GFAP Delta作为人类神经胶质祖细胞的分化标记Cristina Zalfa1, Chiara Grasselli1, Guido Santilli1, Daniela Ferrari1, Giuseppe Lamorte2, Angelo Luigi vescovi1,2,3和Lidia De Filippis3* 1意大利米兰比可卡大学生物技术与生物科学系,米兰科学广场,意大利2意大利罗马,Regina Margherita,意大利3 casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG),意大利*通讯作者:Lidia De Filippis, Casa Sollievo della Sofferenza IRCCS, Viale dei Cappuccini, San Giovanni Rotondo (FG),意大利,电话:+39(0882)410346;电子邮件:lidia.defilippis@unimib.it;l.defilippis@operapadrepio.it收于2018年8月03日;2018年9月11日录用;引用本文:Zalfa C, Grasselli C, Santilli G, Ferrari D, Lamorte G等。(2018)GFAP Delta作为人类神经胶质祖细胞的分化标记。中国生物医学工程学报,38(2):437。doi: 10.4172/2157-7633.1000437版权所有:©2018 Zalfa C等。这是一篇根据知识共享署名许可协议发布的开放获取文章,该协议允许在任何媒体上不受限制地使用、分发和复制,前提是要注明原作者和来源。
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