A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells
A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells
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DOI：
10.1073/pnas.0509789103
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发表时间：
2006-04-11
影响因子：
11.1
通讯作者：
Nakahata, T
中科院分区：
文献类型：
--
作者：
Kato, T;Heike, T;Nakahata, T
尽管胚胎干细胞（ES细胞）能够无限增殖和多能分化，但尚未实现从ES细胞有效制备神经干细胞。在这里，我们已经直接产生下与游离的原代神经球细胞在无血清培养基中的共培养，并观察到相同的效果时，ES细胞与条件培养基的原代神经球培养（CMPNC）。ES-神经干细胞（NSCs）在体外和体内均可增殖7倍以上，并可分化为神经元、星形胶质细胞和少突胶质细胞。通过基质辅助激光解吸/电离飞行时间质谱法确认了CMPNC中的负责分子，结果证明是半胱氨酸蛋白酶抑制剂C。纯化的cystatin C替代CMPNC可有效地培养具有自我更新和多向分化潜能的ES-NSCs。这些结果揭示了胱抑素C用于从ES细胞产生NSC的有效性。
Although embryonic stem (ES) cells are capable of unlimited proliferation and pluripotent differentiation, effective preparation of neural stem cells from ES cells are not achieved. Here, we have directly generated under the coculture with dissociated primary neurosphere cells in serum-free medium and the same effect was observed when ES cells were cultured with conditioned medium of primary neurosphere culture (CMPNC). ES-neural stem cells (NSCs) could proliferate for more than seven times and differentiate into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. The responsible molecule in CMPNC was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, which turned out to be cystatin C. Purified cystatin C in place of the CMPNC could generate ES-NSCs efficiently with self-renewal and multidifferentiation potentials. These results reveal the validity of cystatin C for generating NSCs from ES cells.