Document Detail

The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes.
MedLine Citation:
PMID:  21725321     Owner:  NLM     Status:  MEDLINE    
The transcription factors that regulate differentiation into the monocyte subset in bone marrow have not yet been identified. Here we found that the orphan nuclear receptor NR4A1 controlled the differentiation of Ly6C- monocytes. Ly6C- monocytes, which function in a surveillance role in circulation, were absent from Nr4a1-/- mice. Normal numbers of myeloid progenitor cells were present in Nr4a1-/- mice, which indicated that the defect occurred during later stages of monocyte development. The defect was cell intrinsic, as wild-type mice that received bone marrow from Nr4a1-/- mice developed fewer patrolling monocytes than did recipients of wild-type bone marrow. The Ly6C- monocytes remaining in the bone marrow of Nr4a1-/- mice were arrested in S phase of the cell cycle and underwent apoptosis. Thus, NR4A1 functions as a master regulator of the differentiation and survival of 'patrolling' Ly6C- monocytes.
Richard N Hanna; Leo M Carlin; Harper G Hubbeling; Dominika Nackiewicz; Angela M Green; Jennifer A Punt; Frederic Geissmann; Catherine C Hedrick
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-07-03
Journal Detail:
Title:  Nature immunology     Volume:  12     ISSN:  1529-2916     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-10-07     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  778-85     Citation Subset:  IM    
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MeSH Terms
Antigens, Ly / immunology*
Apoptosis / immunology*
Bone Marrow / immunology*
Cell Cycle / immunology
Cell Differentiation / immunology*
DNA Damage / immunology
Flow Cytometry
Mice, Inbred C57BL
Mice, Knockout
Monocytes / immunology*
Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics,  immunology*
RNA, Messenger / chemistry,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Specific Pathogen-Free Organisms
Grant Support
G0900867//Medical Research Council; R01 HL071141/HL/NHLBI NIH HHS; R01 HL071141/HL/NHLBI NIH HHS; R01 HL071141-07/HL/NHLBI NIH HHS; R01 HL071141-08/HL/NHLBI NIH HHS; R01 HL079621/HL/NHLBI NIH HHS; R01 HL079621/HL/NHLBI NIH HHS; R01 HL079621-03/HL/NHLBI NIH HHS; R01 HL079621-04/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antigens, Ly; 0/Ly-6C antigen, mouse; 0/Nr4a1 protein, mouse; 0/Nuclear Receptor Subfamily 4, Group A, Member 1; 0/RNA, Messenger
Comment In:
Nat Immunol. 2011 Aug;12(8):727-9   [PMID:  21772283 ]

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