Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells
Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells
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DOI：
10.1016/j.stemcr.2017.12.012
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发表时间：
2018-02-13
影响因子：
5.9
通讯作者：
Butler, Samantha J.
中科院分区：
文献类型：
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作者：
Gupta, Sandeep;Sivalingam, Daniel;Butler, Samantha J.
用于神经病症的细胞替代疗法使用人胚胎干细胞（hESC）或诱导多能干细胞（hiPSC）衍生的神经元来替代受损或患病的神经元群体。对于脊髓，已经取得了重大进展，产生恢复协调运动所需的体外衍生运动神经元。然而，目前还没有产生体外衍生的感觉中间神经元（INs）的协议，允许感知环境。在这里，我们报告了一种定向分化方案的发展，以获得hESC和hiPSC的感觉IN。两个发育相关的因素，视黄酸结合骨形态发生蛋白4，可用于产生三类感觉IN：本体感觉dI1s，dI2s和机械感觉dI3s。该方案的关键是神经祖细胞的能力状态，其随时间变化。该方案将有助于开发细胞替代疗法，以重建受伤患者的感觉连接。
Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients.