Gard A L, Pfeiffer S E
Department of Microbiology, University of Connecticut Medical School, Farmington 06030.
Dev Biol. 1993 Oct;159(2):618-30. doi: 10.1006/dbio.1993.1269.
The oligodendrocyte lineage in cerebrum is characterized by the expression of immunologically identified surface antigens resulting in the sequential appearance of three distinct phenotypes, A2B5+O4-, O4+GalC-, and O4+GalC+. In the present study we have placed O4+GalC- progenitors immunopanned from premyelinating rat cerebrum into a basal, defined medium that by itself does not support well either their proliferation or survival. The response of these progenitor cells to platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) was then examined. The results demonstrate that both PDGF and bFGF stimulated proliferation and short-term survival of newly cultured cells, but that their effect on the course of O4+GalC- differentiation was strikingly different. PDGF delayed postmitotic development by transiently reverting (ED50 = 3 ng/ml) O4+GalC- progenitors to A2B5+O4- preprogenitor-like cells that subsequently differentiated even in the continued presence of PDGF. bFGF restored mitogenic activity of the O4+GalC- progenitors to a saturable level at low doses (ED50 = 1 ng/ml); doses of bFGF > or = 10 ng/ml impaired differentiation of the progenitors into GalC+ cells and were also mitogenic for newly differentiated GalC+ oligodendrocytes. These data imply that bFGF supplants PDGF as a mitogen during lineage progression from A2B5+O4- to O4+GalC- progenitors. Lineage reversion of O4+GalC- cells in response to PDGF is suggested as a mechanism for facilitating remyelination by triggering the proliferative expansion of O4+GalC- progenitor-like cells persisting into adulthood.
大脑中的少突胶质细胞谱系的特征是表达可通过免疫鉴定的表面抗原，从而依次出现三种不同的表型：A2B5 + O4 -、O4 + GalC - 和O4 + GalC +。在本研究中，我们将从未成熟大鼠大脑中通过免疫淘选获得的O4 + GalC - 祖细胞置于一种基础的、限定培养基中，该培养基本身对它们的增殖或存活支持效果不佳。然后检测了这些祖细胞对血小板衍生生长因子（PDGF）和碱性成纤维细胞生长因子（bFGF）的反应。结果表明，PDGF和bFGF均刺激新培养细胞的增殖和短期存活，但它们对O4 + GalC - 分化过程的影响却显著不同。PDGF通过将O4 + GalC - 祖细胞短暂逆转（ED50 = 3 ng/ml）为A2B5 + O4 - 前祖细胞样细胞来延迟有丝分裂后的发育，这些细胞随后即使在持续存在PDGF的情况下也会分化。低剂量（ED50 = 1 ng/ml）的bFGF将O4 + GalC - 祖细胞的促有丝分裂活性恢复到饱和水平；bFGF剂量≥10 ng/ml会损害祖细胞向GalC + 细胞的分化，并且对新分化的GalC + 少突胶质细胞也有促有丝分裂作用。这些数据表明，在从A2B5 + O4 - 祖细胞到O4 + GalC - 祖细胞的谱系进展过程中，bFGF取代PDGF作为有丝分裂原。O4 + GalC - 细胞对PDGF的谱系逆转被认为是一种机制，通过触发持续到成年期的O4 + GalC - 祖细胞样细胞的增殖性扩增来促进髓鞘再生。
