期刊
DEVELOPMENT
卷 140, 期 4, 页码 780-788出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.085035
关键词
Thymic epithelial cell; Cbx4; Thymic hypoplasia; T-lymphopoiesis; p63 (Trp63); Polycomb; Epithelial progenitor
资金
- Ministry of Science and Technology of China [2011CB946100]
- National Science Foundation of China [90919061, 81261130314, 30830091]
- National Institutes of Health (USA) [AR049778]
- Engineering and Physical Sciences Research Council [EP/K004204/1, EP/G042365/1] Funding Source: researchfish
- Medical Research Council [MR/K008870/1] Funding Source: researchfish
- EPSRC [EP/K004204/1, EP/G042365/1] Funding Source: UKRI
- MRC [MR/K008870/1] Funding Source: UKRI
Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development.
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