Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation.
BMI-1 and EZH2 Polycomb-group (PcG) proteins belong to two distinct protein complexes involved in the regulation of hematopoiesis. Using unique PcG-specific antisera and triple immunofluorescence, we found that mature resting peripheral T cells expressed BMI-1, whereas dividing blasts were EZH2(+). By contrast, subcapsular immature double-negative (DN) (CD4(-)/CD8(-)) T cells in the thymus coexpressed BMI-1 and EZH2 or were BMI-1 single positive. Their descendants, double-positive (DP; CD4(+)/CD8(+)) cortical thymocytes, expressed EZH2 without BMI-1. Most EZH2(+) DN and DP thymocytes were dividing, while DN BMI-1(+)/EZH2(-) thymocytes were resting and proliferation was occasionally noted in DN BMI-1(+)/EZH2(+) cells. Maturation of DP cortical thymocytes to single-positive (CD4(+)/CD8(-) or CD8(+)/CD4(-)) medullar thymocytes correlated with decreased detectability of EZH2 and continued relative absence of BMI-1. Our data show that BMI-1 and EZH2 expression in mature peripheral T cells is mutually exclusive and linked to proliferation status, and that this pattern is not yet established in thymocytes of the cortex and medulla. T cell stage-specific PcG expression profiles suggest that PcG genes contribute to regulation of T cell differentiation. They probably reflect stabilization of cell type-specific gene expression and irreversibility of lineage choice. The difference in PcG expression between medullar thymocytes and mature interfollicular T cells indicates that additional maturation processes occur after thymocyte transportation from the thymus.
Raaphorst
F M
FM
Department of Pathology, Vrÿe Universiteit University Hospital, Amsterdam, The Netherlands. fm.raaphorst@azvu.nl
Otte
A P
AP
van Kemenade
F J
FJ
Blokzijl
T
T
Fieret
E
E
Hamer
K M
KM
Satijn
D P
DP
Meijer
C J
CJ
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D029721:Drosophila Proteins; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*
C069077:BMI1 protein, human; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C083329:E(z) protein, Drosophila; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1