期刊
NATURE BIOTECHNOLOGY
卷 35, 期 2, 页码 154-163出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3777
关键词
-
资金
- Starr Foundation [NS084334, R01NS072381]
- NYSTEM [C030137, C028128, C029153, C024175]
- Rockefeller University
- NIH Cancer Center [P30 CA008748]
- Starr Foundation
- NYSTEM fellowships [C026879]
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 to rapidly differentiate 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 six 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 d 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据