Preprint / Version 1

Signaling center-guided human gastruloids progress toward early organogenesis

This article is a preprint and has not been certified by peer review.

Authors

    Bin Wang,  
    Bin Wang
    Hanwen Yu,  
    Hanwen Yu
    Ruiyang Li,  
    Ruiyang Li
    Junhua Chen,   Wenjin Ye,   Xiaoyu Wang,  
    Xiaoyu Wang
    Dairui Li,   Huanyao Liu,   Jierui Chen,   Yili Wei,  
    Yili Wei
    Shanshan Huang,  
    Shanshan Huang
    Lan Wei,   Zihao Li,   Chaoying Wen,   Jiacheng Deng,  
    Jiacheng Deng
    Qiumin Chen,   Tao Wang,  
    Tao Wang
    Zhipeng Tan,   Dongjun Lin,   Bruce T. Lahn,  
    Bruce T. Lahn
    Lili Chen,  
    Lili Chen
    • Sun Yat-sen University image/svg+xml
    • Guangdong Provincial Key Laboratory of Stomatology
    Jichang Wang,  
    Jichang Wang
    Andy Peng Xiang,  
    Andy Peng Xiang
    Weiqiang Li
    Weiqiang Li
Categories
Developmental Biology & Anatomy
Keywords
gastruloid; stem cell; organogenesis; signaling center

Abstract

The transition from gastrulation to early organogenesis represents a pivotal milestone in embryogenesis, yet remains poorly understood due to limited access to human models. Inspired by the organizing activity of signaling centers in embryonic development, including the Spemann-Mangold organizer, we present a self-organizing human gastruloid model driven by a WNT/NODAL-induced signaling center. With minimal external input, this center triggers a developmental cascade involving anterior-posterior symmetry breaking, axial elongation, and germ layer specification. Upon extended culture, the model exhibits early organogenic features, including neural development, and the spontaneous co-emergence of contractile cardiac-like structures accompanied by primitive endothelial networks. Single-cell RNA sequencing maps the model’s cell populations onto human developmental references spanning gastrulation and early organogenesis. By re-emphasizing signaling asymmetry as an organizing principle, this platform provides a simple, ethically compliant, and experimentally tractable window into early multilineage organogenesis and enables investigation of how signaling centers contribute to human developmental patterning.

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2026-08-26

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Wang, B., Yu, H., Li, R., Chen, J., Ye, W., Wang, X., Li, D., Liu, H., Chen, J., Wei, Y., Huang, S., Wei, L., Li, Z., Wen, C., Deng, J., Chen, Q., Wang, T., Tan, Z., Lin, D., … Li, W. (2026). Signaling center-guided human gastruloids progress toward early organogenesis. LangTaoSha Preprint Server. https://doi.org/10.65215/LTSpreprints.2026.08.25.000317

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