嗜碱细胞和肥大细胞分化的MYB增强子引导分析

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.