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PMID:23362346
Citation |
Liu, B, Liu, YF, Du, YR, Mardaryev, AN, Yang, W, Chen, H, Xu, ZM, Xu, CQ, Zhang, XR, Botchkarev, VA, Zhang, Y and Xu, GL (2013) Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development 140:780-8 |
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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. |
Links |
PubMed PMC3557775 Online version:10.1242/dev.085035 |
Keywords |
Animals; Bromodeoxyuridine; Cell Proliferation; Epithelial Cells/metabolism; Epithelial Cells/physiology; Flow Cytometry; Gene Expression Regulation, Developmental/genetics; Gene Expression Regulation, Developmental/physiology; Gene Targeting; Histological Techniques; Immunoprecipitation; Mice; Microscopy, Fluorescence; Organogenesis/physiology; Phosphoproteins/metabolism; Polycomb Repressive Complex 1/metabolism; Real-Time Polymerase Chain Reaction; T-Lymphocytes/cytology; Thymus Gland/cytology; Thymus Gland/embryology; Trans-Activators/metabolism; Ubiquitin-Protein Ligases/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
GO:0050673: epithelial cell proliferation |
ECO:0000315: |
P |
According to figure 3A and B, the proliferation of the putative TEC progenitors is independent of Cbx4. |
complete | ||||
involved_in |
GO:0050673: epithelial cell proliferation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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