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用温度敏感型致癌基因永生化的神经胶质前体细胞系,在移植到中枢神经系统的脱髓鞘损伤部位后,可分化为星形胶质细胞和少突胶质细胞。

Lines of glial precursor cells immortalised with a temperature-sensitive oncogene give rise to astrocytes and oligodendrocytes following transplantation into demyelinated lesions in the central nervous system.

作者信息

Trotter J, Crang A J, Schachner M, Blakemore W F

机构信息

Department of Neurobiology, University of Heidelberg, Germany.

出版信息

Glia. 1993 Sep;9(1):25-40. doi: 10.1002/glia.440090105.

DOI:10.1002/glia.440090105
PMID:8244529
Abstract

Immortalised lines of murine glial precursor cells expressing the neomycin resistance gene and a temperature-sensitive mutation of the SV 40 T oncogene were established from cultures of oligodendrocytes and precursor cells infected with a replication-incompetent, helper-free retrovirus. At the permissive temperature (33 degrees C), they could be continually propagated in vitro and cells were present expressing the 04 antigen specific for glial precursor cells and oligodendrocytes. At 38 degrees C, where the expression of the T antigen is down regulated, cell division largely ceased. During early passage in vitro, limited differentiation to a more mature phenotype, as evidenced by expression of GFAP and the oligodendrocyte marker 01 was observed at both 33 degrees C and 38 degrees C. When transplanted into demyelinating lesions in the spinal cords of adult rats early passages of the lines yielded myelin-forming oligodendrocytes and astrocytes. Cells from later passages of the lines although failing to synthesise myelin still associated specifically with the demyelinated axons. These experiments demonstrate the retention of physiological properties of these oncogene-carrying glial cells when transplanted in vivo and suggest that such immortalised populations can be used for the isolation of molecules regulating glial cell function.

摘要

利用无复制能力、无辅助病毒的逆转录病毒感染少突胶质细胞和前体细胞培养物,建立了表达新霉素抗性基因和SV40 T癌基因温度敏感突变的永生化小鼠神经胶质前体细胞系。在允许温度(33摄氏度)下,它们可在体外持续传代培养,且存在表达神经胶质前体细胞和少突胶质细胞特异性04抗原的细胞。在38摄氏度时,T抗原表达下调,细胞分裂基本停止。在体外早期传代过程中,在33摄氏度和38摄氏度时均观察到有限程度的向更成熟表型分化,表现为GFAP和少突胶质细胞标志物01的表达。当将该细胞系的早期传代细胞移植到成年大鼠脊髓的脱髓鞘损伤部位时,可产生形成髓鞘的少突胶质细胞和星形胶质细胞。该细胞系后期传代的细胞虽然不能合成髓鞘,但仍能特异性地与脱髓鞘轴突相关联。这些实验证明了这些携带癌基因的神经胶质细胞在体内移植时保留了生理特性,并表明这种永生化细胞群体可用于分离调节神经胶质细胞功能的分子。

相似文献

1
Lines of glial precursor cells immortalised with a temperature-sensitive oncogene give rise to astrocytes and oligodendrocytes following transplantation into demyelinated lesions in the central nervous system.用温度敏感型致癌基因永生化的神经胶质前体细胞系,在移植到中枢神经系统的脱髓鞘损伤部位后,可分化为星形胶质细胞和少突胶质细胞。
Glia. 1993 Sep;9(1):25-40. doi: 10.1002/glia.440090105.
2
In vitro and in vivo characterisation of glial cells immortalised with a temperature sensitive SV40 T antigen-containing retrovirus.用含温度敏感型SV40 T抗原的逆转录病毒永生化的神经胶质细胞的体外和体内特性分析
J Neurosci Res. 1994 Feb 1;37(2):182-96. doi: 10.1002/jnr.490370204.
3
Embryonic-derived glial-restricted precursor cells (GRP cells) can differentiate into astrocytes and oligodendrocytes in vivo.胚胎来源的胶质细胞限制前体细胞(GRP细胞)在体内可分化为星形胶质细胞和少突胶质细胞。
Exp Neurol. 2001 Sep;171(1):11-21. doi: 10.1006/exnr.2001.7729.
4
Differentiation of the O-2A progenitor cell line CG-4 into oligodendrocytes and astrocytes following transplantation into glia-deficient areas of CNS white matter.将O-2A祖细胞系CG-4移植到中枢神经系统白质的胶质细胞缺乏区域后,其向少突胶质细胞和星形胶质细胞的分化。
Glia. 1995 Jan;13(1):39-44. doi: 10.1002/glia.440130105.
5
The effect of oncogenes on the growth and differentiation of oligodendrocyte type 2 astrocyte progenitor cells.癌基因对少突胶质细胞2型星形胶质细胞祖细胞生长和分化的影响。
Cell Growth Differ. 1995 Jan;6(1):69-80.
6
Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells.通过移植纯化的少突胶质前体细胞修复脱髓鞘病变
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Glial cell transplants that are subsequently rejected can be used to influence regeneration of glial cell environments in the CNS.随后被排斥的胶质细胞移植可用于影响中枢神经系统中胶质细胞环境的再生。
Glia. 1995 Feb;13(2):79-91. doi: 10.1002/glia.440130202.
8
Transplanted neural stem/progenitor cells generate myelinating oligodendrocytes and Schwann cells in spinal cord demyelination and dysmyelination.移植的神经干细胞/祖细胞在脊髓脱髓鞘和髓鞘形成异常中产生形成髓鞘的少突胶质细胞和施万细胞。
Exp Neurol. 2008 Sep;213(1):176-90. doi: 10.1016/j.expneurol.2008.05.024. Epub 2008 Jun 10.
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Failure to achieve remyelination of demyelinated rat axons following transplantation of glial cells obtained from the adult human brain.移植从成人大脑中获取的神经胶质细胞后,脱髓鞘大鼠轴突未能实现髓鞘再生。
Neuropathol Appl Neurobiol. 1996 Jun;22(3):199-206.
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Comparative biochemical, morphological, and immunocytochemical studies between C-6 glial cells of early and late passages and advanced passages of glial cells derived from aged mouse cerebral hemispheres.来自老年小鼠大脑半球的神经胶质细胞早期传代、晚期传代及高级传代的C-6神经胶质细胞之间的比较生化、形态学和免疫细胞化学研究。
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引用本文的文献

1
Don't fence me in: harnessing the beneficial roles of astrocytes for spinal cord repair.不要束缚我:利用星形胶质细胞在脊髓修复中的有益作用。
Restor Neurol Neurosci. 2008;26(2-3):197-214.
2
A quantitative morphometric analysis of rat spinal cord remyelination following transplantation of allogenic Schwann cells.同种异体雪旺细胞移植后大鼠脊髓再髓鞘化的定量形态计量分析
J Comp Neurol. 2002 Feb 11;443(3):259-74. doi: 10.1002/cne.10117.
3
Effects of cyclic AMP on expression of myelin genes in the N20.1 oligodendroglial cell line.环磷酸腺苷对N20.1少突胶质细胞系中髓鞘基因表达的影响。
Neurochem Res. 1998 Mar;23(3):435-41. doi: 10.1023/a:1022430122082.
4
Glial lineages and myelination in the central nervous system.中枢神经系统中的神经胶质谱系与髓鞘形成
J Anat. 1997 Feb;190 ( Pt 2)(Pt 2):161-200. doi: 10.1046/j.1469-7580.1997.19020161.x.
5
Transplanting oligodendrocyte progenitors into the adult CNS.将少突胶质前体细胞移植到成年中枢神经系统中。
J Anat. 1997 Jan;190 ( Pt 1)(Pt 1):23-33. doi: 10.1046/j.1469-7580.1997.19010023.x.
6
Physiological relevance and functional potential of central nervous system-derived cell lines.中枢神经系统来源细胞系的生理相关性和功能潜力。
Mol Neurobiol. 1996 Feb;12(1):13-38. doi: 10.1007/BF02740745.
7
Brain repair.脑部修复。
J R Coll Physicians Lond. 1994 Mar-Apr;28(2):107-20.
8
Transplantation of an oligodendrocyte cell line leading to extensive myelination.移植一种少突胶质细胞系可导致广泛的髓鞘形成。
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11616-20. doi: 10.1073/pnas.91.24.11616.
9
Repair of demyelinated lesions by glial cell transplantation.通过胶质细胞移植修复脱髓鞘病变
J Neurol. 1994 Dec;242(1 Suppl 1):S61-3. doi: 10.1007/BF00939245.
10
Brain repair: an overview.脑修复:概述
J Neurol. 1994 Dec;242(1 Suppl 1):S1-4. doi: 10.1007/BF00939230.