Journal article
Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2
- Abstract:
- Thymic T cell development and T cell receptor repertoire selection are dependent on essential molecular cues provided by thymic epithelial cells (TEC). TEC development and function are regulated by their epigenetic landscape, in which the repressive H3K27me3 epigenetic marks are catalyzed by polycomb repressive complex 2 (PRC2). Here we show that a TEC-targeted deficiency of PRC2 function results in a hypoplastic thymus with reduced ability to express antigens and select a normal repertoire of T cells. The absence of PRC2 activity reveals a transcriptomically distinct medullary TEC lineage that incompletely off-sets the shortage of canonically-derived medullary TEC whereas cortical TEC numbers remain unchanged. This alternative TEC development is associated with the generation of reduced TCR diversity. Hence, normal PRC2 activity and placement of H3K27me3 marks are required for TEC lineage differentiation and function and, in their absence, the thymus is unable to compensate for the loss of a normal TEC scaffold.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 4.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-021-24158-w
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 12
- Article number:
- 3933
- Publication date:
- 2021-06-24
- Acceptance date:
- 2021-05-31
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Keywords:
- Pubs id:
-
1180016
- Local pid:
-
pubs:1180016
- Deposit date:
-
2021-06-02
Terms of use
- Copyright holder:
- Barthlott et al.
- Copyright date:
- 2021
- Rights statement:
- © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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