Journal article
Establishment of a microwell-array-based miniaturized thymic organoid model suitable for high-throughput applications
- Abstract:
- T cell development depends critically on the thymic stroma-in particular, the diverse array of functionally distinct thymic epithelial cell (TEC) types. However, a robust in vitro thymus model mimicking the native thymus and compatible with medium-/high-throughput analyses is currently lacking. Here, we demonstrate a high-density microwell-array-based miniaturized thymus organoid (mTO) model that supports T cell commitment and development, possesses key organizational characteristics of the native thymus, and is compatible with live imaging and medium-/high-throughput applications. We establish the minimum cellular input required for a functional mTO and show that mTO TEC phenotype and complexity closely mirror those of the native thymus. Finally, we use an mTO to probe the role of fetal thymic mesenchyme, revealing a requirement beyond maintenance of Foxn1 in differentiation/maintenance of mature TEC sub-populations. Collectively, mTOs present an in vitro model of the native thymus adaptable to medium-/high-throughput applications and validated for exploration of thymus and thymus organoid biology.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Supplementary materials, zip, 26.6MB, Terms of use)
-
(Preview, Version of record, pdf, 7.7MB, Terms of use)
-
- Publisher copy:
- 10.1016/j.celrep.2025.115579
Authors
+ European Union
More from this funder
- Funder identifier:
- https://ror.org/019w4f821
- Grant:
- 602587
- Programme:
- Seventh Framework Programme (FP7/2007–2013) project ThymiStem
+ Wellcome Trust
More from this funder
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 211944/Z/18/Z
+ UK Research and Innovation
More from this funder
- Funder identifier:
- https://ror.org/001aqnf71
- Grant:
- MR/N013166/1
- BB/MO16412/1
- NC/X002470/1
- MR/T029765/1
+ National Centre for the Replacement Refinement and Reduction of Animals in Research
More from this funder
- Funder identifier:
- https://ror.org/02w0kg036
- Publisher:
- Cell Press
- Journal:
- Cell Reports More from this journal
- Volume:
- 44
- Issue:
- 5
- Article number:
- 115579
- Place of publication:
- United States
- Publication date:
- 2025-04-15
- Acceptance date:
- 2025-03-27
- DOI:
- EISSN:
-
2211-1247
- ISSN:
-
2639-1856
- Pmid:
-
40244847
- Language:
-
English
- Keywords:
- Pubs id:
-
2120559
- Local pid:
-
pubs:2120559
- Deposit date:
-
2025-05-16
- ARK identifier:
Terms of use
- Copyright holder:
- Major et al.
- Copyright date:
- 2025
- Rights statement:
- © 2025 The Authors. Published by Elsevier Inc. User License: Creative Commons Attribution (CC BY 4.0).
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record