Gouti Mina, Delile Julien, Stamataki Despina, Wymeersch Filip J, Huang Yali, Kleinjung Jens, Wilson Valerie, Briscoe James
The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK; Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Dev Cell. 2017 May 8;41(3):243-261.e7. doi: 10.1016/j.devcel.2017.04.002. Epub 2017 Apr 27.
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.
由细胞外信号调控的转录网络控制细胞命运决定，并决定发育中组织的大小和组成。一个例子是控制双能神经中胚层祖细胞（NMPs）的网络，这些祖细胞通过产生脊髓和躯干中胚层组织来推动胚胎伸长。在这里，我们使用单细胞转录组学来识别NMPs的分子特征，并反向设计调节其分化的机制。结合基因扰动，这揭示了一个整合相反视黄酸（RA）和Wnt信号的转录网络，以确定细胞进入和退出NMP状态的速率。新生成的中胚层细胞产生的RA提供反馈，启动NMP的产生并诱导神经分化，从而协调神经和中胚层组织的产生。总之，这些数据定义了一种调节网络结构，该结构平衡了双能祖细胞产生不同细胞类型的过程，以促进轴的有序伸长。
