A Myb enhancer-guided analysis of basophil and mast cell differentiation

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 and Toshio Suda ()
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Takayoshi Matsumura: National University of Singapore
Haruhito Totani: National University of Singapore
Yoshitaka Gunji: Jichi Medical University
Masahiro Fukuda: Duke-NUS Medical School
Rui Yokomori: National University of Singapore
Jianwen Deng: National University of Singapore
Malini Rethnam: National University of Singapore
Chong Yang: National University of Singapore
Tze King Tan: National University of Singapore
Tadayoshi Karasawa: Jichi Medical University
Kazuomi Kario: Jichi Medical University School of Medicine
Masafumi Takahashi: Jichi Medical University
Motomi Osato: National University of Singapore
Takaomi Sanda: National University of Singapore
Toshio Suda: National University of Singapore

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34906-1

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DOI: 10.1038/s41467-022-34906-1

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