Analysis of alternative splicing profiles and the role of RBM47 in myeloid maturation
Myeloid leukocytes, such as neutrophils and monocytes, are critical for innate immunity. As splicing defects are common in malignancies that disrupt myeloid maturation, we hypothesise that alternative splicing (AS) programmes are important in regulating myelopoiesis. To study AS during human neu...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
| Published: |
Nanyang Technological University
2024
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| Online Access: | https://hdl.handle.net/10356/175904 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | Myeloid leukocytes, such as neutrophils and monocytes, are critical for
innate immunity. As splicing defects are common in malignancies that
disrupt myeloid maturation, we hypothesise that alternative splicing (AS)
programmes are important in regulating myelopoiesis. To study AS
during human neutrophil differentiation, HL-60 myeloid leukaemia cells
were used as a model, where an increase in differential cassette exon
events associated with non-productive mRNA isoforms was observed.
Additionally, being primarily expressed in the neutrophilic and monocytic
lineages among leukocytes, the role of the splicing factor RBM47 in
myelopoiesis was examined, with HL-60 cells overexpressing RBM47
exhibiting enhancements in vitamin D3-induced monocytic differentiation
and hundreds of AS changes. Furthermore, the re-analysis of human
myeloid cell RNA-seq datasets revealed that exons neighbouring high
GC-content introns were preferentially upregulated or downregulated in
several datasets. Overall, several AS trends associated with myeloid
maturation was examined, along with the putative myelopoietic
regulatory role of RBM47. |
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