Foxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells.
Foxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells.
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DOI：
10.1038/ncomms7778
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发表时间：
2015-04-14
影响因子：
16.6
通讯作者：
Novitch, Bennett G.
中科院分区：
文献类型：
--
作者：
Adams, Katrina L.;Rousso, David L.;Umbach, Joy A.;Novitch, Bennett G.
脊髓运动神经元（MN）控制各种运动任务，包括呼吸、姿势和运动，这些运动任务被神经退行性疾病（如肌萎缩性侧索硬化症和脊髓性肌萎缩症）破坏。已经开发了指导来自干细胞的MN分化的方法以实现体外疾病建模。然而，大多数协议只产生一个有限的子集的内源性MN亚型。在这里，我们证明了肢体支配的横向运动柱（LMC）MNs可以有效地产生从小鼠和人类胚胎干细胞通过操纵转录因子Foxp1。Foxp1编程的MN表现出内侧和外侧LMC MN的特征，包括表达特定的运动池标志物和轴突导向受体。重要的是，他们优先项目轴突对肢体肌肉外植体在体外和远端肢体肌肉在体内移植后，真正的LMC MN的标志。这些结果为从干细胞产生特定的MN群体用于研究MN发育和疾病提供了有效的方法。 从小鼠和人胚胎干细胞分化脊髓运动神经元（MN）提供了对MN发育和疾病建模的机会，但大多数方案仅产生体内发现的MN亚型的子集。在这里，作者表明，肢体突出的横向运动柱MN可以有效地产生通过表达Foxp1。
Spinal motor neurons (MNs) control diverse motor tasks including respiration, posture and locomotion that are disrupted by neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Methods directing MN differentiation from stem cells have been developed to enable disease modelling in vitro. However, most protocols produce only a limited subset of endogenous MN subtypes. Here we demonstrate that limb-innervating lateral motor column (LMC) MNs can be efficiently generated from mouse and human embryonic stem cells through manipulation of the transcription factor Foxp1. Foxp1-programmed MNs exhibit features of medial and lateral LMC MNs including expression of specific motor pool markers and axon guidance receptors. Importantly, they preferentially project axons towards limb muscle explants in vitro and distal limb muscles in vivo upon transplantation–hallmarks of bona fide LMC MNs. These results present an effective approach for generating specific MN populations from stem cells for studying MN development and disease. The differentiation of spinal motor neurons (MNs) from mouse and human embryonic stem cells provides opportunities to model MN development and disease, but most protocols produce only a subset of the MN subtypes found in vivo. Here the authors show that limb projecting lateral motor column MNs can be efficiently generated though the expression of Foxp1.
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影响因子：
6
作者：
Al Theys, P;Peeters, E;Robberecht, W
通讯作者：
Robberecht, W
DOI：
10.1523/jneurosci.2528-10.2010
发表时间：
2010-10-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Beurg M;Michalski N;Safieddine S;Bouleau Y;Schneggenburger R;Chapman ER;Petit C;Dulon D
通讯作者：
Dulon D
影响因子：
9.8
作者：
Gaber ZB;Butler SJ;Novitch BG
通讯作者：
Novitch BG
影响因子：
16.2
作者：
Haase, G;Dessaud, E;deLapeyrière, O
通讯作者：
deLapeyrière, O
影响因子：
16.2
作者：
Garcia, Natalia V. De Marco;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.