Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression

Title
Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression
Author
정일엽
Keywords
cord blood; eosinophil; RNA-seq; MBP; MMP25
Issue Date
2016-05
Publisher
FEDERATION AMER SOC EXP BIOL
Citation
JOURNAL OF LEUKOCYTE BIOLOGY, v. 100, NO 4, Page. 711-723
Abstract
Oligodendrocyte transcription factor 2, a basic helix-loop-helix transcription factor that binds to E-box motifs, is known to have a key role in determining lineage specification of oligodendrocytes and motor neurons. In the present study, we report that oligodendrocyte transcription factor 2 is expressed in human eosinophils and involved in transcriptional activation of the gene encoding sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), a late eosinophil-differentiation marker known to exert eosinophil apoptosis. When cord blood CD34(+) hematopoietic stem cells differentiated toward eosinophils during a 24-d culture period, oligodendrocyte transcription factor 2 protein was expressed in cord blood eosinophils on d 24, a time when cord blood eosinophils are considered fully differentiated, whereas it was not detectable on d 18 or at earlier time points. Oligodendrocyte transcription factor 2 protein was also abundantly expressed in human peripheral-blood eosinophils but not in neutrophils, monocytes, lymphocytes, or cord blood mast cells. RNA sequencing analysis showed that numerous genes, especially those encoding eosinophil surface molecules, were highly up-regulated along with OLIG2. Among the genes examined, SIGLEC-8 messenger RNA and protein were markedly downregulated in parallel with OLIG2 by an oligodendrocyte transcription factor 2 small interfering RNA or a short hairpin RNA, as evidenced by real-time polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. In reporter gene and chromatin immunoprecipitation experiments, an E-box in the first intron was found to stimulate SIGLEC-8 gene transcription and to bind oligodendrocyte transcription factor 2. Hence, at least one important aspect of eosinophil differentiation is regulated by oligodendrocyte transcription factor 2, a transcription factor that has not previously been reported, to our knowledge, in normal granulocytes.
URI
https://jlb.onlinelibrary.wiley.com/doi/abs/10.1189/jlb.1A0715-314RRRhttp://repository.hanyang.ac.kr/handle/20.500.11754/71418
ISSN
0741-5400; 1938-3673
DOI
10.1189/jlb.1A0715-314RRR
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GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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