A Myb Enhancer-guided Analysis of Basophil and Mast Cell Differentiation (Nat Commun, Nov 22)

/ 2022, Latest Happenings, Research / By

Takayoshi Matsumura 1 2 3, Haruhito Totani 4, Yoshitaka Gunji 5, Masahiro Fukuda 6 7, Rui Yokomori 4, Jianwen Deng 4, Malini Rethnam 4, Chong Yang 4, Tze King Tan 4, Tadayoshi Karasawa 5, Kazuomi Kario 8, Masafumi Takahashi 5, Motomi Osato 4, Takaomi Sanda 4 9, Toshio Suda 10 11 12

Affiliations

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. csitkm@nus.edu.sg.
  • 2Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan. csitkm@nus.edu.sg.
  • 3Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan. csitkm@nus.edu.sg.
  • 4Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • 5Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
  • 6Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
  • 7International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • 8Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan.
  • 9Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 10Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. sudato@keio.jp.
  • 11International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan. sudato@keio.jp.
  • 12Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. sudato@keio.jp.

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.

PMID: 36400777  DOI: 10.1038/s41467-022-34906-1

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