An atlas of early human mandibular endochondral and osteogenic paracrine signaling regions of Meckel's cartilage

• 成果类型: Article
• 署名作者: Shen, Zongshan; Zhang, Ran; Chen, Xinyue; Yang, Guan; Si, Yuanchun; Yan, Tianxing; Chen, Suwen; Cheng, Bin; Wu, Xiaoshan; Chen, Di; Zhang, Dong; Xiao, Guozhi; Zhu, Jian-Kang; Wang, Songlin
• 署名单位: Capital Medical University; Capital Medical University; Sun Yat Sen University; Peking University; Capital Medical University; Central South University; Shenzhen University of Advanced Technology; Southern University of Science & Technology; Southern University of Science & Technology; Southern University of Science & Technology; Southern University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12725
• DOI: 10.1073/pnas.2420466122
• 发表日期: 2025-03-25
• 关键词: growth

摘要

The mandible, also known as the lower jaw, is the only bone in the skull that can move and is essential for speaking and chewing. Meckel's cartilage (MC) is a temporary structure that supports the formation of the mandible, but how MC is involved in the ossification of the mandible is poorly understood. Through the use of single-cell RNA sequencing and single-cell spatial transcriptomics analyses, a spatiotemporal atlas of MC in human fetuses from 7 to 15 wk postconception was established, highlighting the role of MC in the ossification of the mandible. Importantly, we revealed that two populations of MC contributed to mandibular ossification through different mechanisms. The anterior MC can differentiate into osteolineage cells, as shown in an in vivo lineage tracing mouse model. The intermediate MC facilitates intramembranous ossification through cell-cell communications, possibly through signaling ligands like BMP5, BMP7, SEMA3A, PDGFC, and FGF7. This study suggests that MC plays a crucial role in mediating mandibular ossification through distinct mechanisms, providing valuable insights for understanding oral and craniofacial diseases and disorders in the future.