方案摘要
方案下载| 应用领域 | 生物产业 |
| 检测样本 | 其他 |
| 检测项目 | |
| 参考标准 | 无 |
Takayoshi Matsumura, Haruhito Totani, Yoshitaka Gunji, Masahiro Fukuda, Rui Yokomori, Jianwen Deng, Malini Rethnam, Chong Yang, Tze King Tan, Tadayoshi Karasawa, Kazuomi Kario, Masafumi Takahashi, Motomi Osato, Takaomi Sanda & Toshio Suda Abstract The transcription factor MYB is a crucial regulator of hematopoietic stem and progenitor cells. However, the nature of lineage-specific enhancer usage of the Myb gene is largely unknown. We identify the Myb ?68 enhancer, a regulatory element which marks basophils and mast cells. Using the Myb ?68 enhancer activity, we show a population of granulocyte-macrophage progenitors with higher potential to differentiate into basophils and mast cells. Single cell RNA-seq demonstrates the differentiation trajectory is continuous from progenitors to mature basophils in vivo, characterizes bone marrow cells with a gene signature of mast cells, and identifies LILRB4 as a surface marker of basophil maturation. Together, our study leads to a better understanding of how MYB expression is regulated in a lineage-associated manner, and also shows how a combination of lineage-related reporter mice and single-cell transcriptomics can overcome the rarity of target cells and enhance our understanding of gene expression programs that control cell differentiation in vivo.
转录因子MYB是造血干细胞和祖细胞的一个重要调控因子。然而，MYB基因的线粒体特异性增强子的使用性质在很大程度上是未知的。我们确定了MYB -68增强子，这是一个标记嗜碱细胞和肥大细胞的调节元件。利用MYB -68增强子的活性，我们显示了一群粒细胞-巨噬细胞祖细胞具有更高的分化为嗜碱细胞和肥大细胞的潜力。单细胞RNA-seq显示分化轨迹在体内从祖细胞到成熟嗜碱细胞是连续的，描述了具有肥大细胞基因特征的骨髓细胞，并确定LILRB4是嗜碱细胞成熟的表面标志。总之，我们的研究使我们更好地理解了MYB的表达是如何以系谱相关的方式被调控的，同时也显示了系谱相关的报告小鼠和单细胞转录组学的结合可以克服目标细胞的稀有性，并加强我们对控制体内细胞分化的基因表达程序的理解。
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