| 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
|
| Resource |
| Human and Animal Cells |
201B7(HPS0063)
409B2(HPS0076)
1383D6(HPS1006) |
