Dynamic intron retention modulates gene expression in the monocytic differentiation pathway

Renhua Song, Shweta Tikoo, Rohit Jain, Natalia Pinello, Amy Ym Au, Rajini Nagarajah, Bo Porse, John E J Rasko, Justin J-L Wong

2 Citations (Scopus)

Abstract

Monocytes play a crucial role in maintaining homeostasis and mediating a successful innate immune response. They also act as central players in diverse pathological conditions, thus making them an attractive therapeutic target. Within the bone marrow, monocytes arise from a committed precursor termed Common Monocyte Progenitor (cMoP). However, molecular mechanisms that regulate the differentiation of cMoP to various monocytic subsets remain unclear. Herein, we purified murine myeloid precursors for deep poly-A-enriched RNA sequencing to understand the role of alternative splicing in the development and differentiation of monocytes under homeostasis. Our analyses revealed intron retention to be the major alternative splicing mechanism involved in the monocyte differentiation cascade, especially in the differentiation of Ly6Chi monocytes to Ly6Clo monocytes. Furthermore, we found that the intron retention of key genes involved in the differentiation of murine Ly6Chi to Ly6Clo monocytes was also conserved in humans. Our data highlight the unique role of intron retention in the regulation of the monocytic differentiation pathway.

Original languageEnglish
JournalImmunology
Volume165
Issue number2
Pages (from-to)274-286
Number of pages13
ISSN0019-2805
DOIs
Publication statusPublished - Feb 2022

Keywords

  • bioinformatics
  • haematopoiesis
  • monocytes
  • transcriptomics

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