biostudies-literatureMatsumura TMOH | National Medical Research CouncilMEXT | Japan Society for the Promotion of ScienceNOVARTIS Foundation (Japan) for the Promotion of Science (NOVARTIS FoundationDaiwa Securities Health Foundation7064https://www.ebi.ac.uk/biostudies/studies/S-EPMC9674656biostudies-literatureUnknown13(1)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.Nature communicationsA Myb enhancer-guided analysis of basophil and mast cell differentiation.PMC9674656NMRC/CNIG/1155/2016JP21K19514Fukuda MDeng JRethnam MMatsumura TYang CKarasawa TYokomori RSuda TOsato MTan TKTotani HGunji YSanda TTakahashi MKario KfalseA Myb enhancer-guided analysis of basophil and mast cell differentiation.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.2022-01-01T00:00:00Z2022 Nov2026-05-27T11:56:38.379Z2025-04-19T06:03:31.992ZS-EPMC96746563640077710.1038/s41467-022-34906-1