Alternative splicing in human myeloid cell differentiation

Alternative splicing (AS) plays a pivotal role in the differentiation of immune cells and regulates immune responses. Dysregulations in splicing have been linked to abnormal cell function and can result in diseases. As splicing factors (SFs) are critical in AS, this project aims to understand the ro...

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Main Author: Lee, Trena Wan Xuan
Other Authors: Francesc Xavier Roca Castella
Format: Final Year Project (FYP)
Language:English
Published: Nanyang Technological University 2022
Subjects:
Online Access:https://hdl.handle.net/10356/163700
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author Lee, Trena Wan Xuan
author2 Francesc Xavier Roca Castella
author_facet Francesc Xavier Roca Castella
Lee, Trena Wan Xuan
author_sort Lee, Trena Wan Xuan
collection NTU
description Alternative splicing (AS) plays a pivotal role in the differentiation of immune cells and regulates immune responses. Dysregulations in splicing have been linked to abnormal cell function and can result in diseases. As splicing factors (SFs) are critical in AS, this project aims to understand the role of RNA-binding motif protein 47 (RBM47), a SF, in myeloid cell differentiation. Human promyelocytic leukaemia (HL-60) cells were used as a model for monocyte-like and neutrophil-like differentiation. Differentially expressed genes (DEGs) and differential alternative splicing events (DASEs) associated with RBM47 overexpression were identified from RNA sequencing data. RBM47 overexpression was observed to upregulate a large pool of DEGs when these cells were treated with vitamin D3. Six notable DEGs were selected for further experiments. Monocyte-differentiated HL-60 with overexpressed RBM47 had increased ROS production and surface expression of myeloid maturation and monocytic markers. DASEs were validated in three genes. Findings from this project suggest that RBM47 overexpression supports myeloid cell differentiation in HL-60, resulting in more mature myeloid phenotypes, though more work is required before conclusions can be drawn.
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spelling ntu-10356/1637002023-02-28T18:09:37Z Alternative splicing in human myeloid cell differentiation Lee, Trena Wan Xuan Francesc Xavier Roca Castella School of Biological Sciences xroca@ntu.edu.sg Science::Biological sciences Alternative splicing (AS) plays a pivotal role in the differentiation of immune cells and regulates immune responses. Dysregulations in splicing have been linked to abnormal cell function and can result in diseases. As splicing factors (SFs) are critical in AS, this project aims to understand the role of RNA-binding motif protein 47 (RBM47), a SF, in myeloid cell differentiation. Human promyelocytic leukaemia (HL-60) cells were used as a model for monocyte-like and neutrophil-like differentiation. Differentially expressed genes (DEGs) and differential alternative splicing events (DASEs) associated with RBM47 overexpression were identified from RNA sequencing data. RBM47 overexpression was observed to upregulate a large pool of DEGs when these cells were treated with vitamin D3. Six notable DEGs were selected for further experiments. Monocyte-differentiated HL-60 with overexpressed RBM47 had increased ROS production and surface expression of myeloid maturation and monocytic markers. DASEs were validated in three genes. Findings from this project suggest that RBM47 overexpression supports myeloid cell differentiation in HL-60, resulting in more mature myeloid phenotypes, though more work is required before conclusions can be drawn. Bachelor of Science in Biological Sciences 2022-12-14T12:21:34Z 2022-12-14T12:21:34Z 2022 Final Year Project (FYP) Lee, T. W. X. (2022). Alternative splicing in human myeloid cell differentiation. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/163700 https://hdl.handle.net/10356/163700 en application/pdf Nanyang Technological University
spellingShingle Science::Biological sciences
Lee, Trena Wan Xuan
Alternative splicing in human myeloid cell differentiation
title Alternative splicing in human myeloid cell differentiation
title_full Alternative splicing in human myeloid cell differentiation
title_fullStr Alternative splicing in human myeloid cell differentiation
title_full_unstemmed Alternative splicing in human myeloid cell differentiation
title_short Alternative splicing in human myeloid cell differentiation
title_sort alternative splicing in human myeloid cell differentiation
topic Science::Biological sciences
url https://hdl.handle.net/10356/163700
work_keys_str_mv AT leetrenawanxuan alternativesplicinginhumanmyeloidcelldifferentiation