Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells.
Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells.
复制标题
DOI：
10.1093/jmcb/mjab076
复制
发表时间：
2022-02-24
影响因子：
5.5
通讯作者：
Li WL
中科院分区：
文献类型：
--
作者：
Zhang GY;Lv ZM;Ma HX;Chen Y;Yuan Y;Sun PX;Feng YQ;Li YW;Lu WJ;Yang YD;Yang C;Yu XL;Wang C;Liang SL;Zhang ML;Li HL;Li WL
脊髓损伤包括运动神经元变性和脱髓鞘，可导致终生残疾，但恢复神经功能的有效临床干预措施尚未开发出来。在脊髓发育的早期，由少突胶质细胞转录因子2(OLIG2)的表达决定的运动神经元(PMN)域的神经前体细胞首先在腹侧脊髓产生运动神经元，然后改变命运产生髓鞘形成的少突胶质细胞。鉴于其分化潜能，PMN前体细胞可能成为治疗相关神经疾病(如脊髓损伤)的有价值的细胞来源。然而，到目前为止，在保持其分化潜能的同时，快速培养和扩增PMN前体细胞在技术上是具有挑战性的。在这项研究中，我们在化学筛选的基础上，开发了一种新的配方，可以有效地从人胚胎干细胞中诱导出PMN前体细胞。更重要的是，这些OLIG2+PMN前体细胞可以稳定地维持多代，而不会失去快速产生脊髓运动神经元和少突胶质细胞的能力。我们的结果表明，这些自我更新的PMN前体细胞有可能成为治疗脊髓损伤和脱髓鞘疾病的可再生细胞移植来源。
Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.
登录
查看更多内容
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：
5.9
作者：
Douvaras, Panagiotis;Wang, Jing;Zimmer, Matthew;Hanchuk, Stephanie;O'Bara, Melanie A.;Sadiq, Saud;Sim, Fraser J.;Goldman, James;Fossati, Valentina
通讯作者：
Fossati, Valentina
影响因子：
5.3
作者：
Jakovcevski, I;Zecevic, N
通讯作者：
Zecevic, N
影响因子：
5.3
作者：
Li, Saiqun;Mattar, Pierre;Schuurmans, Carol
通讯作者：
Schuurmans, Carol
影响因子：
23.9
作者：
Piao, Jinghua;Major, Tamara;Auyeung, Gordon;Policarpio, Edelweiss;Menon, Jayanthi;Droms, Leif;Gutin, Philip;Uryu, Kunihiro;Tchieu, Jason;Soulet, Denis;Tabar, Viviane
通讯作者：
Tabar, Viviane