轉(zhuǎn)錄因子ThPOK(由Zbtb7b編碼)作為胸腺中CD4細(xì)胞譜系的主要調(diào)節(jié)因子而廣為人知。在這里，研究人員報告了ThPOK作為髓系譜系的形成，分化和成熟的多方面調(diào)節(jié)因子的一個意想不到的和關(guān)鍵的作用。利用報告基因和敲除小鼠模型，結(jié)合單細(xì)胞RNA測序、祖細(xì)胞轉(zhuǎn)移和集落分析，研究人員表明，ThPOK在穩(wěn)態(tài)分化期間控制單核細(xì)胞-樹突狀細(xì)胞和粒細(xì)胞譜系的生成，并且通過改變信使RNA剪接來重編程內(nèi)含子保留，通過對譜系特異性轉(zhuǎn)錄因子和RNA的轉(zhuǎn)錄調(diào)節(jié)，在粒細(xì)胞譜系特異性細(xì)胞中充當(dāng)中性粒細(xì)胞成熟的制動器。

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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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