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Polycomb Repressive Complex 2 is essential for development and maintenance of a functional TEC compartment.
Nandini Singarapu1, Keyue Ma2, Kaitlin A G Reeh1
1Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, Texas, 78957, USA.
Scientific Reports
|September 27, 2018
Summary
Thymic epithelial cell (TEC) development requires Polycomb repressive complex 2 (PRC2) activity. Downregulating Tbx1 in early thymus progenitors is crucial for proper PRC2 function and TEC maturation.
Area of Science:
- Developmental Biology
- Epigenetics
- Immunology
Background:
- Thymic epithelial cells (TECs) are vital for T cell development and selection.
- Molecular mechanisms guiding TEC development from third pharyngeal pouch (3rd PP) endoderm remain unclear.
- TBX1 transcription factor negatively regulates TEC development.
Purpose of the Study:
- Investigate the role of Polycomb repressive complex 2 (PRC2) in TEC development.
- Determine how TBX1 influences TEC development and PRC2 activity.
- Elucidate the molecular interplay between TBX1 and PRC2 in the thymus.
Main Methods:
- Utilized conditional knockout mouse models (Foxn1Cre) to delete Eed, a key PRC2 component.
- Analyzed TEC proliferation and differentiation in Eed conditional knockout (EedCKO) mutants.
- Compared gene expression profiles of EedCKO TEC with TEC ectopically expressing Tbx1.
Main Results:
- Ectopic Tbx1 expression in TECs increased PRC2 target gene expression, suggesting interference with PRC2.
- Deletion of Eed in thymus-fated endoderm disrupted TEC proliferation and differentiation, leading to dysplastic thymi.
- A significant overlap was observed between differentially expressed genes in EedCKO TEC and TEC with ectopic Tbx1 expression.
Conclusions:
- PRC2 is essential for normal TEC development.
- Downregulation of Tbx1 in thymus-fated 3rd PP endoderm is necessary for optimal PRC2 function.
- TBX1 may regulate TEC development by modulating PRC2 activity.
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