Modeling Human Spine-Spinal Cord Organogenesis by hPSC-Derived Neuromesodermal Progenitors

Author:

Li Dairui,Ma Yuanchen,Huang Weijun,Li Xiaoping,Liu Huanyao,Xiong Chuanfeng,Zhao Qi,Wang Bin,Lai Xingqiang,Huang Shanshan,Wei Yili,Chen Junhua,Zhang Xiyu,Wei Lan,Ye Wenjin,Chen Qiumin,Rong LiminORCID,Xiang Andy Peng,Li WeiqiangORCID

Abstract

AbstractHuman trunk development, including spine and spinal cord organogenesis, is a coordinated, orderly, and interdependent process with spatiotemporal tissue patterning. However, the underlying cellular and molecular mechanisms remain largely unclear due to the lack of an effective model that can simulate the early development of human body axis. Here, we reported the long-term patterning and dynamic morphogenesis of human trunk through the formation of spine-spinal cord organoids (SSCOs) self-organized from three-dimensional culture of human PSC-derived neuromesodermal progenitors (NMPs). The SSCOs resembled the morphogenetic features of spine and spinal cord along the anterior–posterior axis, and showed the chondro-osteogenic and neural trajectories consistent with developmental dynamics of spine and spinal cord in gestational embryo through single-cell RNA sequencing (scRNA-seq). In addition, we identified a new HMMR+ bipotent cell population with self-renewal ability and neural/mesodermal competence but distinct from NMPs, which may be involved in trunk development and represent an invaluable tool for disease modeling of spine- and spinal cord-related disorders.Graphic Abstract

Publisher

Cold Spring Harbor Laboratory

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