Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA.
FASEB J. 2010 Jun;24(6):1925-34. doi: 10.1096/fj.09-150573. Epub 2010 Feb 2.
Thrombospondin 1 (TSP1), an oligomeric matrix protein, is known for its antiangiogenic activity. Recently, TSP1 has been shown to regulate synaptogenesis in the developing brain. In this study, we examine another role of TSP1 in the CNS, namely, in proliferation and differentiation of neural progenitor cells (NPCs). We found that adult mice deficient in TSP1 exhibit reduced proliferation of NPCs in vivo [13,330+/-826 vs. 4914+/-455 (mean+/-se wt vs. TSP1(-/-)); P<0.001, Student's t test] and impaired neuronal differentiation (1382+/-83 vs. 879+/-79; P<0.001). In vitro, NPC obtained from adult TSP1(-/-) mice display decreased proliferation in BrdU assay (48+/-8 vs. 24+/-3.5%; P<0.01) and decreased neuronal fate commitment (8+/-0.85 vs. 4.6+/-0.5%; P<0.05) in contrast to wild-type NPCs. Both proliferation and neuronal differentiation deficits are remediable in vitro by exogenous TSP1. Notably, conditioned medium from TSP1(-/-) astrocytes, unlike that from control astrocytes, fails to promote neurogenesis in wild-type NPCs, suggesting that TSP1 is one of the key molecules responsible for astrocyte-induced neurogenesis. Our data demonstrate that TSP1 is a critical participant in maintenance of the adult NPC pool and in neuronal differentiation.
血小板反应蛋白 1（TSP1）是一种寡聚基质蛋白，以其抗血管生成活性而闻名。最近，TSP1 被证明可调节发育中大脑中的突触发生。在这项研究中，我们研究了 TSP1 在中枢神经系统中的另一个作用，即在神经祖细胞（NPC）的增殖和分化中。我们发现，缺乏 TSP1 的成年小鼠体内 NPC 的增殖减少[13,330+/-826 与 4914+/-455（wt 与 TSP1(-/-)的平均值+/-se；P<0.001，Student's t 检验]，并且神经元分化受损（1382+/-87 与 879+/-79；P<0.001）。在体外，从成年 TSP1(-/-)小鼠中获得的 NPC 在 BrdU 测定中显示增殖减少（48+/-8 与 24+/-3.5%；P<0.01），神经元命运决定减少（8+/-0.85 与 4.6+/-0.5%；P<0.05），与野生型 NPC 相比。与野生型 NPC 相比，外源性 TSP1 可在体外修复增殖和神经元分化缺陷。值得注意的是，与对照星形胶质细胞不同，TSP1(-/-)星形胶质细胞的条件培养基不能促进野生型 NPC 的神经发生，表明 TSP1 是星形胶质细胞诱导神经发生的关键分子之一。我们的数据表明，TSP1 是维持成年 NPC 池和神经元分化的关键参与者。
