A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.
A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.
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DOI：
10.1016/j.devcel.2017.04.002
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发表时间：
2017-05-08
影响因子：
11.8
通讯作者：
Briscoe J
中科院分区：
文献类型：
--
作者：
Gouti M;Delile J;Stamataki D;Wymeersch FJ;Huang Y;Kleinjung J;Wilson V;Briscoe J
转录网络受细胞外信号调节，控制细胞命运决定并决定发育组织的大小和组成。一个例子是控制双能神经中胚层祖细胞（NMP）的网络，该网络通过生成脊髓和躯干中胚层组织来促进胚胎伸长。在这里，我们使用单细胞转录组学来识别 NMP 的分子特征，并对调节其分化的机制进行逆向工程。与遗传扰动一起，这揭示了一个转录网络，该网络整合了相反的视黄酸 (RA) 和 Wnt 信号，以确定细胞进入和退出 NMP 状态的速率。 RA 由新生成的中胚层细胞产生，提供启动 NMP 生成并诱导神经分化的反馈，从而协调神经和中胚层组织的生成。这些数据共同定义了一个调节网络架构，该架构平衡双能祖细胞不同细胞类型的生成，以促进有序的轴伸长。单细胞 RNA 测序揭示了神经中胚层祖细胞的特征 体外 NMP 与体内对应物相似并具有相似的分化 视黄酸信号在 NMP 诱导和神经分化中的双重作用 转录网络调节神经与中胚层分配 神经中胚层祖细胞 (NMP) 生成脊髓和体节细胞。古蒂等人。证明体外 NMP 在单细胞水平上与体内对应物相似，并定义了一个调节网络，平衡神经和中胚层组织的生成，以促进胚胎轴的有序延伸。
Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation. Single-cell RNA-seq reveals a signature of neuromesodermal progenitors In vitro NMPs resemble and differentiate similar to their in vivo counterparts Dual role for retinoic acid signaling in NMP induction and neural differentiation A transcriptional network regulates neural versus mesodermal allocation Neuromesodermal progenitors (NMPs) generate cells of the spinal cord and somites. Gouti et al. demonstrate that in vitro NMPs resemble in vivo counterparts at the single-cell level and define a regulatory network that balances the generation of neural and mesodermal tissue to facilitate orderly extension of the embryonic axis.