转录因子ThPOK(由Zbtb7b编码)作为胸腺中CD4细胞谱系的主要调节因子而广为人知。在这里,研究人员报告了ThPOK作为髓系谱系的形成,分化和成熟的多方面调节因子的一个意想不到的和关键的作用。利用报告基因和敲除小鼠模型,结合单细胞RNA测序、祖细胞转移和集落分析,研究人员表明,ThPOK在稳态分化期间控制单核细胞-树突状细胞和粒细胞谱系的生成,并且通过改变信使RNA剪接来重编程内含子保留,通过对谱系特异性转录因子和RNA的转录调节,在粒细胞谱系特异性细胞中充当中性粒细胞成熟的制动器。
原文:
The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.
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