Reference - Detail
| RRC ID | 85629 |
|---|---|
| Author | Pretemer Y, Gao Y, Kanai K, Yamamoto T, Kometani K, Ozaki M, Nishigishi K, Ikeda T, Xu H, Hotta A, Hamazaki Y. |
| Title | An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification. |
| Journal | Nat Commun |
| Abstract |
Thymic epithelial cells (TEC) are crucial in supporting T cell development, but their high heterogeneity and difficulty of isolation pose obstacles to their study in humans. Particularly, how diverse TEC lineages arise from a common progenitor remains poorly understood. To address this, here we establish a human iPSC-based model of thymus organogenesis capable of deriving these lineages in vitro. Through controlled retinoid signaling followed by self-directed differentiation, we obtain FOXN1+ TEC progenitor-like cells and diverse mature MHCII+ populations resembling cortical and medullary TECs, allowing us to infer their developmental trajectories. Upon thymocyte co-culture, induced TECs support the generation of naïve T cells with diverse TCR repertoires and further develop into AIRE+ and mimetic TEC subpopulations. Our system provides a fully in vitro model of human TEC differentiation from early fate specification to late-stage maturation, offering new insights into human thymus development and potential regenerative applications for congenital thymic disorders. |
| Volume | 16(1) |
| Pages | 7680 |
| Published | 2025-8-25 |
| DOI | 10.1038/s41467-025-62523-1 |
| PII | 10.1038/s41467-025-62523-1 |
| PMID | 40855082 |
| PMC | PMC12378236 |
| MeSH | AIRE Protein Cell Differentiation Cell Lineage* Coculture Techniques Epithelial Cells* / cytology Epithelial Cells* / metabolism Forkhead Transcription Factors / metabolism Humans Induced Pluripotent Stem Cells* / cytology Induced Pluripotent Stem Cells* / metabolism Models, Biological Organogenesis T-Lymphocytes / cytology Thymocytes / cytology Thymocytes / metabolism Thymus Gland* / cytology Thymus Gland* / metabolism Transcription Factors / metabolism |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 35 |
| Altmetric score changes over past 6months | 1.0 |
| Resource | |
| Human and Animal Cells | 201B7(HPS0063) 409B2(HPS0076) 1383D6(HPS1006) |