Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells.
Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells.
复制标题
DOI：
10.1038/nbt.3777
复制
发表时间：
2017-03
影响因子：
46.9
通讯作者：
Studer L
中科院分区：
文献类型：
--
作者：
Qi Y;Zhang XJ;Renier N;Wu Z;Atkin T;Sun Z;Ozair MZ;Tchieu J;Zimmer B;Fattahi F;Ganat Y;Azevedo R;Zeltner N;Brivanlou AH;Karayiorgou M;Gogos J;Tomishima M;Tessier-Lavigne M;Shi SH;Studer L
在将人类多能干细胞（hPSC）转化为功能性神经元方面已经取得了相当大的进展。然而，人类神经元特化和功能成熟的时间延长仍然是阻碍hPSC衍生谱系在疾病建模和再生医学中的常规应用的关键挑战。使用组合小分子筛选，我们先前确定了hPSC快速分化为外周感觉神经元的条件。在这里，我们概括的方法，中枢神经系统（CNS）的命运，通过开发一个小分子的方法，加速诱导早期出生的皮层神经元。在没有神经胶质细胞共培养的情况下，6种通路抑制剂的组合应用诱导分化第16天具有功能性电生理特性的有丝分裂后皮质神经元。在分化8天时移植到出生后小鼠皮层中的所得神经元是功能性的，并建立长距离投射，如使用iDISCO全脑成像所示。加速分化为皮质神经元的命运，应促进hPSC为基础的战略，疾病建模和细胞治疗中枢神经系统疾病。
Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders.
登录
查看更多内容
影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
从人类多能干细胞中衍生出多种释放激素的垂体细胞。
影响因子：
5.9
作者：
Zimmer B;Piao J;Ramnarine K;Tomishima MJ;Tabar V;Studer L
通讯作者：
Studer L
影响因子：
16.6
作者：
Du, Zhong-Wei;Chen, Hong;Liu, Huisheng;Lu, Jianfeng;Qian, Kun;Huang, CindyTzu-Ling;Zhong, Xiaofen;Fan, Frank;Zhang, Su-Chun
通讯作者：
Zhang, Su-Chun
影响因子：
46.9
作者：
Maury, Yves;Come, Julien;Nedelec, Stephane
通讯作者：
Nedelec, Stephane
影响因子：
11.4
作者：
Greber, Boris;Coulon, Philippe;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.