Linker histone H1.2 and H1.4 affect the neutrophil lineage determination

Gabriel Sollberger (Lead / Corresponding author), Robert Streeck, Falko Apel, Brian E. Caffrey, Arthur I. Skoultchi, Arturo Zychlinsky

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Abstract

Neutrophils are important innate immune cells that tackle invading pathogens with different effector mechanisms. They acquire this antimicrobial potential during their maturation in the bone marrow, where they differentiate from hematopoietic stem cells in a process called granulopoiesis. Mature neutrophils are terminally differentiated and short-lived with a high turnover rate. Here, we show a critical role for linker histone H1 on the differentiation and function of neutrophils using a genome-wide CRISPR/Cas9 screen in the human cell line PLB-985. We systematically disrupted expression of somatic H1 subtypes to show that individual H1 subtypes affect PLB-985 maturation in opposite ways. Loss of H1.2 and H1.4 induced an eosinophil-like transcriptional program, thereby negatively regulating the differentiation into the neutrophil lineage. Importantly, H1 subtypes also affect neutrophil differentiation and the eosinophil-directed bias of murine bone marrow stem cells, demonstrating an unexpected subtype-specific role for H1 in granulopoiesis.
Original languageEnglish
Article numbere52563
Pages (from-to)1-24
Number of pages24
JournaleLife
Volume9
Early online date11 May 2020
DOIs
Publication statusPublished - 27 May 2020

Keywords

  • H1 linker histone
  • cell differentiation
  • developmental biology
  • hematopoiesis
  • human
  • immunology
  • inflammation
  • innate immunity
  • lineage determination
  • mouse
  • neutrophil

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    Sollberger, G., Streeck, R., Apel, F., Caffrey, B. E., Skoultchi, A. I., & Zychlinsky, A. (2020). Linker histone H1.2 and H1.4 affect the neutrophil lineage determination. eLife, 9, 1-24. [e52563]. https://doi.org/10.7554/eLife.52563