Molecular analysis of the midbrain dopaminergic niche during neurogenesis
Molecular analysis of the midbrain dopaminergic niche during neurogenesis
复制标题
神经发生过程中脑多巴胺能生态位的分子分析
DOI：
10.1101/155846
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
E. Arenas
中科院分区：
文献类型：
--
作者：
E. Toledo;G. L. Manno;P. R. D. V. Cervo;Daniel Gyllborg;Saiful Islam;Carlos Villaescusa;S. Linnarsson;E. Arenas
中脑多巴胺能(MDA)神经元在帕金森病中变性，是细胞替代疗法的主要靶点之一。然而，对促进丙二醛神经发生的信号和细胞类型的全面观察尚不清楚。通过在组织和单细胞水平上分析小鼠腹侧中脑在丙二醛神经发生过程中的转录组，我们发现最近发现的三个放射状胶质细胞类型1-3(Rgl1-3)在丙二醛神经发生的不同关键方面起作用。Rgl3表达最多的细胞外基质成分和多种调控MDA神经元发育途径的配体，如Wnt和Shh，Rgl1-2表达最多的受体。此外，我们发现，特定的转录因子网络解释了转录组，并为每个个体放射状胶质细胞提供了一种功能。在Rgl1中发现了一个控制神经发生的网络，在Rgl2中发现了祖细胞的维持，并在Rgl3中发现了形成丙二醛生态位的因子的分泌。因此，我们的结果揭示了在丙二醛神经发生过程中每种中脑细胞类型表达的发育信号的广泛谱系。被鉴定为其重要性的细胞是Rgl3，一种利基细胞类型，以及Rgl1，一种表达ARNTL的神经源性前体细胞，我们发现ARNTL是丙二醛神经发生所必需的转录因子。
Midbrain dopaminergic (mDA) neurons degenerate in Parkinson’s disease and are one of the main targets for cell replacement therapies. However, a comprehensive view of the signals and cell types contributing to mDA neurogenesis is not yet available. By analyzing the transcriptome of the mouse ventral midbrain at a tissue and single-cell level during mDA neurogenesis we found that three recently identified radial glia types 1-3 (Rgl1-3) contribute to different key aspects of mDA neurogenesis. While Rgl3 expressed most extracellular matrix components and multiple ligands for various pathways controlling mDA neuron development, such as Wnt and Shh, Rgl1-2 expressed most receptors. Moreover, we found that specific transcription factor networks explain the transcriptome and suggest a function for each individual radial glia. A network controlling neurogenesis was found in Rgl1, progenitor maintenance in Rgl2 and the secretion of factors forming the mDA niche by Rgl3. Our results thus uncover a broad repertoire of developmental signals expressed by each midbrain cell type during mDA neurogenesis. Cells identified for their emerging importance are Rgl3, a niche cell type, and Rgl1, a neurogenic progenitor that expresses ARNTL, a transcription factor that we find is required for mDA neurogenesis.
影响因子：
7.2
作者：
Lu P;Takai K;Weaver VM;Werb Z
通讯作者：
Werb Z
影响因子：
11.4
作者：
Pataskar, Abhijeet;Jung, Johannes;Tiwari, Vijay K.
通讯作者：
Tiwari, Vijay K.