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Cbx4 regulates the proliferation of thymic epithelial cells and thymus function.


ABSTRACT: 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.

SUBMITTER: Liu B 

PROVIDER: S-EPMC3557775 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Cbx4 regulates the proliferation of thymic epithelial cells and thymus function.

Liu Bo B   Liu Yuan-Feng YF   Du Ya-Rui YR   Mardaryev Andrei N AN   Yang Wei W   Chen Hui H   Xu Zhi-Mei ZM   Xu Chen-Qi CQ   Zhang Xiao-Ren XR   Botchkarev Vladimir A VA   Zhang Yu Y   Xu Guo-Liang GL  

Development (Cambridge, England) 20130201 4


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  ...[more]

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