Cbx4 regulates the proliferation of thymic epithelial cells and thymus function.
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.
Department of Immunology and Key Laboratory of Medical Immunology of Ministry of Public Health, Peking University Health Science Center, Beijing 100191, China.
Bo
B
Liu
Yuan-Feng
YF
Liu
Ya-Rui
YR
Du
Andrei N
AN
Mardaryev
Wei
W
Yang
Hui
H
Chen
Zhi-Mei
ZM
Xu
Chen-Qi
CQ
Xu
Xiao-Ren
XR
Zhang
Vladimir A
VA
Botchkarev
Yu
Y
Zhang
Guo-Liang
GL
Xu
D000818:Animals; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D006652:Histological Techniques; D047468:Immunoprecipitation; D008025:Ligases; D051379:Mice; D008856:Microscopy, Fluorescence; D038081:Organogenesis / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology*; D015534:Trans-Activators / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D063150:Polycomb Repressive Complex 1; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570504:Cbx4 protein, mouse; D001973:Bromodeoxyuridine