期刊
IMMUNOLOGY
卷 165, 期 2, 页码 274-286出版社
WILEY
DOI: 10.1111/imm.13435
关键词
bioinformatics; haematopoiesis; monocytes; transcriptomics
类别
资金
- National Health and Medical Research Council [1126306, 1128175, 1177305]
- Cancer Council of New South Wales [RG11-11]
- Cure the Future
- Novo Nordisk Foundation [NNF17CC0027852]
- Sydney Catalyst
- Arrow Bone Marrow Transplant Foundation
- National Health and Medical Research Council of Australia [1177305, 1126306, 1128175] Funding Source: NHMRC
Monocytes play a crucial role in immune responses, and the intron retention mechanism during their differentiation pathway is found to be essential in regulating the differentiation process, with distinct intron retention differences observed among different subsets of monocytes.
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.
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