On January 22, 2022, a collaborative team from Fudan University and the Chinese Academy of Medical Sciences published a research paper titled "Modeling human thyroid development by fetal tissue-derived organoid culture" in Advanced Science. This work analyzed human thyroid embryonic development at the single-cell level, identifying the critical time window of 12 to 16 weeks of gestation for thyroid functional maturation and mapping its cellular evolution. The researchers further unveiled the signaling regulatory mechanisms underlying human fetal thyroid development and, based on this, established an organoid culture system that mimics human thyroid functional maturation. This provides an important theoretical and model foundation for research on human thyroid development and prospective medical studies.

Researchers have established human fetal thyroid organoids (hFTOs) for the first time. These organoids not only retain the lineage and molecular characteristics of thyroid tissue at the embryonic stage but also have the ability to produce human thyroid follicles after kidney transplantation in mice. Furthermore, the researchers found that activation of the cAMP signal in the in vitro culture system can induce the maturation of hFTOs into human maturation thyroid organoids (hMTOs) with the ability to secrete thyroid hormones. This process accurately mimics key developmental events in the thyroid. At the single-cell level, the researchers precisely revealed the developmental characteristics of human fetal thyroids and their organoids, capturing thyroid cell subpopulations in a functionally mature state. This helps to uncover the regulatory mechanisms of signals during the thyroid functional developmental stage. Using RNA-seq and ATAC-seq technologies, they explored changes in the transcriptome and chromatin accessibility during the functional development of human fetal thyroid organoids.

The use of human embryonic tissue to establish organoid models for direct study of human tissue and organ development is one of the best ways to investigate real human embryonic development and birth defects, as well as to validate conclusions from animal models. Additionally, it will significantly and sustainably reduce the use of human embryonic tissue and experimental animals.

LIANG Jianqing, a doctoral candidate at the Institute of Human Phenome Sciences, Fudan University, and QIAN Jun, a doctoral candidate at the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, are the co-first authors of the paper. LIN Xinhua, ZHAO Bing, and WANG Xiaoyue are the co-corresponding authors. CHEN Xiaojun, director of the Obstetrics and Gynecology Hospital of Fudan University, and Professor WANG Xiaoning from the School of Laboratory Medicine and Biotechnology, Southern Medical University, provided important guidance for the research. This work was conducted at the Organoid Research Center of the State Key Laboratory of Genetic Engineering at Fudan University. In collaboration with hospitals affiliated with Fudan University, the center has established a germline resource bank of human organoids with clear genetic backgrounds, stable maintenance, and cryopreservation capabilities, covering multiple lineages and cancer types, including normal tissues, embryonic tissues, and progressive tumors. This provides important support for research on human organoid-based development and diseases.