A miR-150/TET3 pathway regulates the generation of mouse and human non-classical monocyte subset

被引:40
作者
Selimoglu-Buet, Dorothee [1 ]
Riviere, Julie [1 ,2 ]
Ghamlouch, Hussein [1 ,2 ]
Bencheikh, Laura [1 ,2 ]
Lacout, Catherine [1 ,2 ]
Morabito, Margot [1 ,2 ]
Diop, M'boyba [3 ]
Meurice, Guillaume [3 ]
Breckler, Marie [3 ]
Chauveau, Aurelie [1 ,4 ]
Debord, Camille [1 ,5 ]
Debeurme, Franck [1 ,2 ]
Itzykson, Raphael [1 ,6 ]
Chapuis, Nicolas [7 ]
Willekens, Christophe [1 ,8 ]
Wagner-Ballon, Orianne [10 ]
Bernard, Olivier A. [1 ,2 ]
Droin, Nathalie [1 ,2 ,3 ]
Solary, Eric [1 ,2 ,9 ]
机构
[1] INSERM, U1170, Gustave Roussy Canc Ctr, F-94805 Villejuif, France
[2] Univ Paris Sud, Fac Med, F-94270 Le Kremlin Bicetre, France
[3] INSERM, US23, CNRS, Gustave Roussy Canc Ctr,UMS 3655, F-94805 Villejuif, France
[4] Ctr Hosp Reg Univ, Lab Hematol, F-29200 Brest, France
[5] Ctr Hosp Reg Univ, Lab Hematol, F-44000 Nantes, France
[6] Hop St Louis, AP HP, Dept Hematol, F-75010 Paris, France
[7] Inst Cochin, Dept Immunohematol, F-75014 Paris, France
[8] Univ Paris Diderot, F-75004 Paris, France
[9] Gustave Roussy Canc Ctr, Dept Hematol, F-94805 Villejuif, France
[10] Hop Henri Mondor, Dept Hematol & Immunol Biol, F-94010 Creteil, France
关键词
CELL FATE; LY6C(LOW) MONOCYTES; DENDRITIC CELLS; STEADY-STATE; C/EBP-BETA; IN-VIVO; DIFFERENTIATION; TRANSCRIPTION; MACROPHAGES; PROGENITOR;
D O I
10.1038/s41467-018-07801-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Non-classical monocyte subsets may derive from classical monocyte differentiation and the proportion of each subset is tightly controlled. Deregulation of this repartition is observed in diverse human diseases, including chronic myelomonocytic leukemia (CMML) in which non-classical monocyte numbers are significantly decreased relative to healthy controls. Here, we identify a down-regulation of hsa-miR-150 through methylation of a lineage-specific promoter in CMML monocytes. Mir150 knock-out mice demonstrate a cell-autonomous defect in non-classical monocytes. Our pulldown experiments point to Ten-Eleven-Translocation-3 (TET3) mRNA as a hsa-miR-150 target in classical human monocytes. We show that Tet3 knockout mice generate an increased number of non-classical monocytes. Our results identify the miR150/TET3 axis as being involved in the generation of non-classical monocytes.
引用
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页数:17
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