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  3. Modeling Human Thyroid Development by Fetal Tissue-Derived Organoid Culture

Modeling Human Thyroid Development by Fetal Tissue-Derived Organoid Culture

  • Adv Sci (Weinh). 2022 Mar;9(9):e2105568. doi: 10.1002/advs.202105568.
Jianqing Liang 1,  Jun Qian 2,  Li Yang 1,  Xiaojun Chen 3,  Xiaoning Wang 4,  Xinhua Lin 1,  Xiaoyue Wang 2,  Bing Zhao 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
  • 2 State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100730, China.
  • 3 Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
  • 4 School of Laboratory Medicine and Biotechnology, Southern Medical University, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510000, China.
PMID: 35064652 DOI: 10.1002/advs.202105568
Abstract

Euthyroidism is of profound importance for lifetime health. However, the early diagnosis or therapeutics of thyroid developmental defects has not been established, mainly due to limited understanding of human thyroid development and a lack of recapitulating research model. Herein, the authors elaborate the cell atlas and potential regulatory signaling of the evolution of heterogeneous thyrocyte population from 12 to 16 gestational weeks. Moreover, they establish a long-term culture of human fetal thyroid organoids (hFTOs) system, which retains the fetal thyroid lineages and molecular signatures, as well as the ability to generate functional human thyroid follicles post mice renal transplantation. Notably, cAMP signaling activation in hFTOs by forskolin boosts the maturation of follicle and thus thyroid hormone T4 secretion, which recapitulates the key developmental events of fetal thyroid. Employing this ex vivo system, it is found that enhanced chromatin accessibility at thyroid maturation genes (such as TPO and TG) loci permits the transcription for hormone production. This study provides the cell atlas of and an Organoid model for human thyroid development, which will facilitate thyroid research and prospective medicine.

Keywords

cAMP signaling; cell atlas; fetal thyroid organoids; human thyroid development; in vitro maturation.

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