Dynamic intron retention modulates gene expression in the monocytic differentiation pathway.

Autor: Song R; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia., Tikoo S; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.; Immune Imaging Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia., Jain R; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.; Immune Imaging Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia., Pinello N; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia., Au AYM; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia., Nagarajah R; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia., Porse B; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Rasko JEJ; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., J-L Wong J; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2022 Feb; Vol. 165 (2), pp. 274-286. Date of Electronic Publication: 2021 Dec 12.
DOI: 10.1111/imm.13435
Abstrakt: 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 Ly6C hi monocytes to Ly6C lo monocytes. Furthermore, we found that the intron retention of key genes involved in the differentiation of murine Ly6C hi to Ly6C lo monocytes was also conserved in humans. Our data highlight the unique role of intron retention in the regulation of the monocytic differentiation pathway.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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