Ishizaki Y, Burne J F, Raff M C
Developmental Neurobiology Programme, Medical Research Council Laboratory for Molecular Cell Biology, University College London, United Kingdom.
J Cell Biol. 1994 Aug;126(4):1069-77. doi: 10.1083/jcb.126.4.1069.
We recently proposed that most mammalian cells other than blastomeres may be programmed to kill themselves unless continuously signaled by other cells not to. Many observations indicate that some mammalian cells are programmed in this way, but is it the case for most mammalian cells? As it is impractical to test all of the hundreds of types of mammalian cells, we have focused on two tissues--lens and cartilage--which each contain only a single cell type: if there are cells that do not require signals from other cells to avoid programmed cell death (PCD), lens epithelial cells and cartilage cells (chondrocytes) might be expected to be among them. We have previously shown that rat lens epithelial cells can survive in serum-free culture without signals from other cell types but seem to require signals from other lens epithelial cells to survive: without such signals they undergo PCD. We show here that the same is true for rat (and chick) chondrocytes. They can survive for weeks in culture at high cell density in the absence of other cell types, serum, or exogenous proteins or signaling molecules, but they die with the morphological features of apoptosis in these conditions at low cell density. Medium from high density cultures, FCS, or a combination of known growth factors, all support prolonged chondrocyte survival in low density cultures, as long as antioxidants are also present. Moreover, medium from high density chondrocyte cultures promotes the survival of lens epithelial cells in low density cultures and vice versa. Chondrocytes isolated from adult rats behave similarly to those isolated from developing rats. These findings support the hypothesis that most mammalian cells require signals from other cells to avoid PCD, although the signals can sometimes be provided by cells of the same type, at least in tissues that contain only one cell type.
我们最近提出，除卵裂球外，大多数哺乳动物细胞可能被编程为自我毁灭，除非不断得到其他细胞发出的不要自我毁灭的信号。许多观察结果表明，一些哺乳动物细胞是以这种方式被编程的，但大多数哺乳动物细胞也是如此吗？由于测试数百种哺乳动物细胞中的每一种都不切实际，我们将重点放在了两种组织——晶状体和软骨——上，这两种组织各自仅包含单一细胞类型：如果存在不需要其他细胞发出信号来避免程序性细胞死亡（PCD）的细胞，晶状体上皮细胞和软骨细胞（软骨细胞）可能就在其中。我们之前已经表明，大鼠晶状体上皮细胞在无血清培养中可以在没有其他细胞类型发出信号的情况下存活，但似乎需要其他晶状体上皮细胞发出的信号才能存活：没有这种信号，它们就会发生程序性细胞死亡。我们在此表明，大鼠（和鸡）软骨细胞也是如此。它们在没有其他细胞类型、血清、外源性蛋白质或信号分子的情况下，在高细胞密度培养中可以存活数周，但在这些条件下，在低细胞密度时它们会以凋亡的形态特征死亡。高密度培养的培养基、胎牛血清（FCS）或已知生长因子的组合，只要同时存在抗氧化剂，都能支持软骨细胞在低密度培养中长时间存活。此外，高密度软骨细胞培养的培养基能促进低密度培养的晶状体上皮细胞存活，反之亦然。从成年大鼠分离的软骨细胞与从发育中的大鼠分离的软骨细胞表现相似。这些发现支持了这样一种假说，即大多数哺乳动物细胞需要其他细胞发出的信号来避免程序性细胞死亡，尽管这些信号有时可以由同一类型的细胞提供，至少在仅包含一种细胞类型的组织中是这样。
