Yuan Yuan, Loh Yong-Hwee Eddie, Han Xia, Feng Jifan, Ho Thach-Vu, He Jinzhi, Jing Junjun, Groff Kimberly, Wu Alan, Chai Yang
Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
Bioinformatics Service, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Sci Adv. 2020 Dec 16;6(51). doi: 10.1126/sciadv.abb0119. Print 2020 Dec.
Cranial neural crest (CNC) cells contribute to different cell types during embryonic development. It is unknown whether postmigratory CNC cells undergo dynamic cellular movement and how the process of cell fate decision occurs within the first pharyngeal arch (FPA). Our investigations demonstrate notable heterogeneity within the CNC cells, refine the patterning domains, and identify progenitor cells within the FPA. These progenitor cells undergo fate bifurcation that separates them into common progenitors and mesenchymal cells, which are characterized by and expression, respectively. The common progenitors undergo further bifurcations to restrict them into osteogenic/odontogenic and chondrogenic/fibroblast lineages. Disruption of a patterning domain leads to specific mandible and tooth defects, validating the binary cell fate restriction process. Different from the compartment model of mandibular morphogenesis, our data redefine heterogeneous cellular domains within the FPA, reveal dynamic cellular movement in time, and describe a sequential series of binary cell fate decision-making process.
颅神经嵴(CNC)细胞在胚胎发育过程中分化为不同的细胞类型。尚不清楚迁移后的CNC细胞是否会发生动态细胞运动,以及在第一咽弓(FPA)内细胞命运决定过程是如何发生的。我们的研究证明了CNC细胞内存在显著的异质性,细化了模式形成区域,并确定了FPA内的祖细胞。这些祖细胞经历命运分歧,将它们分为共同祖细胞和间充质细胞,分别以 和 的表达为特征。共同祖细胞进一步发生分歧,将它们限制为成骨/成牙和软骨形成/成纤维细胞谱系。模式形成区域的破坏会导致特定的下颌骨和牙齿缺陷,验证了二元细胞命运限制过程。与下颌骨形态发生的区室模型不同,我们的数据重新定义了FPA内的异质细胞区域,揭示了细胞随时间的动态运动,并描述了一系列连续的二元细胞命运决策过程。