Generation of neural progenitor cells by chemical cocktails and hypoxia.
Generation of neural progenitor cells by chemical cocktails and hypoxia.
复制标题
通过化学混合物和缺氧产生神经祖细胞
作者：
神经前体细胞（Neural progenitor cells，NPCs）是由体细胞经一定条件诱导而成的。本文报道了在生理性低氧条件下，VCR（VPA，HDACs抑制剂; CHIR 99021，GSK-3激酶抑制剂; Repsox，TGF-β通路抑制剂）可诱导小鼠胚胎成纤维细胞产生NPCs。这些化学诱导的NPC（ciNPC）类似于小鼠脑源性NPC，关于它们的增殖和自我更新能力、基因表达谱以及体外和体内不同神经外胚层谱系的多能性。进一步的实验揭示，具有组蛋白脱乙酰化、糖原合成酶激酶和TGF-β途径的抑制剂的替代混合物显示出对于ciNPC诱导的类似功效。此外，也可以用相同的化学混合物VCR从小鼠尾尖成纤维细胞和人尿细胞诱导ciNPC。因此，我们的研究表明，谱系特异性转换的体细胞的NPC可以实现化学鸡尾酒，而不引入外源性因子。
Neural progenitor cells (NPCs) can be induced from somatic cells by defined factors. Here we report that NPCs can be generated from mouse embryonic fibroblasts by a chemical cocktail, namely VCR (V, VPA, an inhibitor of HDACs; C, CHIR99021, an inhibitor of GSK-3 kinases and R, Repsox, an inhibitor of TGF-β pathways), under a physiological hypoxic condition. These chemical-induced NPCs (ciNPCs) resemble mouse brain-derived NPCs regarding their proliferative and self-renewing abilities, gene expression profiles, and multipotency for different neuroectodermal lineages in vitro and in vivo. Further experiments reveal that alternative cocktails with inhibitors of histone deacetylation, glycogen synthase kinase, and TGF-β pathways show similar efficacies for ciNPC induction. Moreover, ciNPCs can also be induced from mouse tail-tip fibroblasts and human urinary cells with the same chemical cocktail VCR. Thus our study demonstrates that lineage-specific conversion of somatic cells to NPCs could be achieved by chemical cocktails without introducing exogenous factors.
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影响因子：
48
作者：
Kurian, Leo;Sancho-Martinez, Ignacio;Nivet, Emmanuel;Aguirre, Aitor;Moon, Krystal;Pendaries, Caroline;Volle-Challier, Cecile;Bono, Francoise;Herbert, Jean-Marc;Pulecio, Julian;Xia, Yun;Li, Mo;Montserrat, Nuria;Ruiz, Sergio;Dubova, Ilir;Rodriguez, Concepcion;Denli, Ahmet M.;Boscolo, Francesca S.;Thiagarajan, Rathi D.;Gage, Fred H.;Loring, Jeanne F.;Laurent, Louise C.;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
影响因子：
10.5
作者：
DAVIS, CA;JOYNER, AL
通讯作者：
JOYNER, AL
DOI：
10.1073/pnas.1219181110
发表时间：
2012-12-18
影响因子：
11.1
作者：
Li, Wendong;Tian, E.;Shi, Yanhong
通讯作者：
Shi, Yanhong
DOI：
10.1073/pnas.1121003109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Lujan, Ernesto;Chanda, Soham;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
23.9
作者：
Han, Dong Wook;Tapia, Natalia;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.