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脐血祖细胞来源的和成人祖细胞来源的人肥大细胞之间的差异基因表达谱

Differential gene expression profile between cord blood progenitor-derived and adult progenitor-derived human mast cells.

作者信息

Inomata Naoko, Tomita Hisashi, Ikezawa Zenro, Saito Hirohisa

机构信息

Research Unit for Allergy Transcriptome, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

出版信息

Immunol Lett. 2005 May 15;98(2):265-71. doi: 10.1016/j.imlet.2004.12.001. Epub 2005 Jan 4.

Abstract

In order to better understand the mechanisms governing the display of mast cell characteristics in human mast cells (MCs), such as cord blood (CB)-derived cultured mast cells, peripheral blood (PB)-derived cultured MCs, and differentiated adult-lung cultured MCs, we examined the transcriptomes of these three types MCs using oligonucleotide microarray (GeneChip) and hierarchical clustering analysis. The expression profile of CB-derived MCs substantially differed from those of PB- and lung-derived MCs. In CB-derived MCs, we identified 132 up-regulated transcripts, such as MARCKS, KRT1, TIMP2, SERPINA1, and TLR2, and 428 down-regulated transcripts, such as LTBP3, CDC42BPA, DDO, DICER1, and FCER1A. Moreover, using RT-PCR and FACS analysis, we confirmed the expression of TLR2, which plays an important role in innate immunity, in CB-derived MCs but not in PB-derived MCs. In addition, it was observed that CB-derived MCs uniquely release histamine and CCL1, which are produced by human MCs but not by human monocytes, in response to peptidoglycan (PGN), although it had been controversy issue whether CB-derived MCs could, in fact, induce degranulation in response to PGN. These results indicated that in innate immunity MCs derived from neonatal hemopoietic cells might have unique functions compared to their adult counterparts because of different gene profiles.

摘要

为了更好地理解调控人类肥大细胞(MCs)特征表现的机制,比如脐血(CB)来源的培养肥大细胞、外周血(PB)来源的培养MCs以及分化的成人肺培养MCs,我们使用寡核苷酸微阵列(基因芯片)和层次聚类分析研究了这三种类型MCs的转录组。CB来源的MCs的表达谱与PB来源和肺来源的MCs的表达谱有很大差异。在CB来源的MCs中,我们鉴定出132个上调转录本,如MARCKS、KRT1、TIMP2、SERPINA1和TLR2,以及428个下调转录本,如LTBP3、CDC42BPA、DDO、DICER1和FCER1A。此外,通过RT-PCR和FACS分析,我们证实了在先天免疫中起重要作用的TLR2在CB来源的MCs中有表达,但在PB来源的MCs中没有表达。另外,观察到CB来源的MCs在响应肽聚糖(PGN)时会独特地释放组胺和CCL1,这是人类MCs而非人类单核细胞产生的,尽管CB来源的MCs是否真的能响应PGN诱导脱颗粒一直存在争议。这些结果表明,在先天免疫中,源自新生儿造血细胞的MCs由于基因谱不同,可能与其成年对应物具有独特的功能。

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