Expression of myelin transcription factor 1 and lamin B receptor mediate neural progenitor fate transition in the zebrafish spinal cord pMN domain.

Expression of myelin transcription factor 1 and lamin B receptor mediate neural progenitor fate transition in the zebrafish spinal cord pMN domain.
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髓磷脂转录因子1和核纤层蛋白B受体的表达介导斑马鱼脊髓pMN结构域神经祖细胞命运转变

DOI:
10.1016/j.jbc.2022.102452
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发表时间:
2022-10
影响因子:
4.8
通讯作者:
Chen, Gang
Chen, Gang
中科院分区:
生物学2区
文献类型:
--
作者:
Xing, Lingyan;Chai, Rui;Wang, Jiaqi;Lin, Jiaqi;Li, Hanyang;Wang, Yueqi;Lai, Biqin;Sun, Junjie;Chen, Gang

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PMN结构域是腹侧脊髓中的一个限制性结构域,由OLIG2基因的表达定义。尽管已知PMN前体细胞可以顺序地产生运动神经元和少突胶质细胞,但这些前体细胞的谱系存在争议,其后代是如何产生的还不清楚。在这里,我们利用单细胞RNA测序,在斑马鱼中发现了具有不同命运和分子特征的PMN前体细胞之间的一种未知的异质性。值得注意的是,我们使用生物信息学分析表征了两种不同的运动神经元谱系。然后,我们继续研究调节神经前体细胞命运转换的特定分子程序。我们通过实验验证了转录因子myt1(髓鞘转录因子1)和内核膜整合蛋白LBR(lamin B受体)的表达分别对运动神经元的发育和神经前体细胞的维持起着至关重要的作用。我们预计,斑马鱼PMN前体细胞的转录组特征和分子程序不仅将提供对先前关于少突胶质前体细胞和运动神经元谱系分析的深入了解,还将有助于进一步了解神经前体细胞命运转换所涉及的分子编程。
The pMN domain is a restricted domain in the ventral spinal cord, defined by the expression of the olig2 gene. Though it is known that the pMN progenitor cells can sequentially generate motor neurons and oligodendrocytes, the lineages of these progenitors are controversial and how their progeny are generated is not well understood. Using single-cell RNA sequencing, here, we identified a previously unknown heterogeneity among pMN progenitors with distinct fates and molecular signatures in zebrafish. Notably, we characterized two distinct motor neuron lineages using bioinformatic analysis. We then went on to investigate specific molecular programs that regulate neural progenitor fate transition. We validated experimentally that expression of the transcription factor myt1 (myelin transcription factor 1) and inner nuclear membrane integral proteins lbr (lamin B receptor) were critical for the development of motor neurons and neural progenitor maintenance, respectively. We anticipate that the transcriptome features and molecular programs identified in zebrafish pMN progenitors will not only provide an in-depth understanding of previous findings regarding the lineage analysis of oligodendrocyte progenitor cells and motor neurons but will also help in further understanding of the molecular programming involved in neural progenitor fate transition.
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