Molecular signatures and transcriptional regulatory networks of human immature decidual NK and mature peripheral NK cells

Molecular signatures and transcriptional regulatory networks of human immature decidual NK and mature peripheral NK cells
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人类未成熟蜕膜 NK 细胞和成熟外周 NK 细胞的分子特征和转录调控网络

DOI:
10.1002/eji.201344183
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发表时间:
2014-09
期刊:
Eur J Immunol
影响因子:
--
通讯作者:
Haiming
Haiming
中科院分区:
其他
文献类型:
--
作者:
Wang;Fuyan;Zhou;Yonggang;Fu Binqing;Wu;Yang;Zhang;Ruya;Sun;Rui;Tian;Zhigang;Wei;Haiming

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人类未成熟和成熟的自然杀伤(NK)细胞之间存在许多差异,但它们各自的分子特征和转录调节因子相对未知。为了获得对人类 NK 细胞多样性和发育调控的新见解,我们使用经过独立验证的高分辨率微阵列数据来描述具有 CD56brightCD16−T‐bet− 表型的未成熟蜕膜 NK (idNK) 细胞和具有 CD56dimCD16+T-bet+ 表型的成熟外周 NK (mpNK) 细胞之间的全面比较分析。这项研究表明,NK 细胞表达许多新型生长因子、细胞因子和趋化因子,它们可能以自分泌方式调节 NK 细胞的发育或功能。值得注意的是,我们发现 idNK 和 mpNK 细胞分别富含同源框和锌指转录因子(TF)。此外,许多新的候选转录调节因子对于 idNK 和 mpNK 细胞来说是常见的。我们进一步描述了 NK 细胞的转录调控网络,并表明 idNK 细胞中富含的内源生长因子、细胞因子和 TF 相互调节,并可能导致 idNK 细胞不成熟。总之,这些发现为未成熟和成熟 NK 细胞提供了新的分子特征,这里确定的新候选调节因子可用于描述和进一步了解 NK 细胞的分化和功能。
Many differences exist between human immature and mature natural killer (NK) cells, but their respective molecular signatures and transcriptional regulators are relatively unknown. To gain new insights into the diversity and developmental regulation of human NK cells, we used data from high‐resolution microarrays with independent verification to describe a comprehensive comparative analysis between immature decidual NK (idNK) cells with a CD56brightCD16−T‐bet− phenotype and mature peripheral NK (mpNK) cells with a CD56dimCD16+T‐bet+ phenotype. This study shows that many novel growth factors, cytokines, and chemokines are expressed by NK cells, and they may regulate NK‐cell development or function in an autocrine manner. Notably, we present that idNK and mpNK cells are enriched for homeobox and zinc‐finger transcription factors (TFs), respectively. Additionally, many novel candidate transcriptional regulators are common to both idNK and mpNK cells. We further describe the transcriptional regulatory networks of NK cells and show that the endogenous growth factors, cytokines, and TFs enriched in idNK cells regulate each other and may contribute to idNK‐cell immaturity. Together, these findings provide novel molecular signatures for immature and mature NK cells, and the novel candidate regulators identified here can be used to describe and further understand NK‐cell differentiation and function.
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