Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency
Abnormal myelination has been observed across several neurodegenerative conditions, and is hypothesised to be a key factor leading to disease pathophysiology. Here, we investigate early molecular mechanisms leading to abnormal myelination using Ermin deficiency as a model. Ermin is a gene expressed...
| Main Authors: | , , , , , |
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| Format: | Conference Paper |
| Language: | English |
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2024
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| Online Access: | https://hdl.handle.net/10356/173229 https://www.grc.org/myelin-conference/2024/ |
| _version_ | 1824455902943510528 |
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| author | Oh, Sher Li Ziaei, Amin Tan, Liang Juin Utami, Kagistia Hana Pouladi, Mahmoud A. Langley, Sarah Raye |
| author2 | Interdisciplinary Graduate School (IGS) |
| author_facet | Interdisciplinary Graduate School (IGS) Oh, Sher Li Ziaei, Amin Tan, Liang Juin Utami, Kagistia Hana Pouladi, Mahmoud A. Langley, Sarah Raye |
| author_sort | Oh, Sher Li |
| collection | NTU |
| description | Abnormal myelination has been observed across several neurodegenerative conditions, and is hypothesised to be a key factor leading to disease pathophysiology. Here, we investigate early molecular mechanisms leading to abnormal myelination using Ermin deficiency as a model. Ermin is a gene expressed specifically in oligodendrocytes during the late stage of myelination, and its altered expression has been associated with several neurological conditions, including epilepsy, schizophrenia, and a familial form of multiple sclerosis, although its involvement in their pathophysiology is still unclear. We studied the transcriptome of Ermin-deficient mice using gene co-expression and differential gene expression analyses to investigate early transcriptional effects of Ermin deficiency across age and sex. We observed altered expression of transcription factors at early ages, and in protein processing and synaptic function over time. In silico gene perturbation and ChIP-seq analysis were used to elucidate the roles that differentially expressed transcription factors play in oligodendrocyte differentiation and as well as in their effects on protein processing and synaptic function. Finally, we assessed the relationship between early molecular changes in Ermin deficiency in neurological conditions using genome-wide association studies. Our observations suggest that there are common mechanisms between Ermin deficiency and biological processes influenced by genetic variants of genetic generalised epilepsy. Our findings demonstrate that in the Ermin-deficient model of abnormal myelination, early changes in transcription factor expression are associated with dysregulation in oligodendrocyte differentiation, synaptic organisation, and protein modification. These transcriptional changes are also enriched for genetic variants in neurological disease and provide insight into the early molecular mechanisms involving abnormal myelination in neurological disorders. |
| first_indexed | 2025-02-19T03:45:36Z |
| format | Conference Paper |
| id | ntu-10356/173229 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:45:36Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1732292024-03-31T15:38:17Z Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency Oh, Sher Li Ziaei, Amin Tan, Liang Juin Utami, Kagistia Hana Pouladi, Mahmoud A. Langley, Sarah Raye Interdisciplinary Graduate School (IGS) Lee Kong Chian School of Medicine (LKCMedicine) 2024 Myelin Gordon Research Conference (GRC) Translational Laboratory in Genetic Medicine, A*STAR University of British Columbia Cardiff University Medicine, Health and Life Sciences Neurological disorders Ermin deficiency Abnormal myelination has been observed across several neurodegenerative conditions, and is hypothesised to be a key factor leading to disease pathophysiology. Here, we investigate early molecular mechanisms leading to abnormal myelination using Ermin deficiency as a model. Ermin is a gene expressed specifically in oligodendrocytes during the late stage of myelination, and its altered expression has been associated with several neurological conditions, including epilepsy, schizophrenia, and a familial form of multiple sclerosis, although its involvement in their pathophysiology is still unclear. We studied the transcriptome of Ermin-deficient mice using gene co-expression and differential gene expression analyses to investigate early transcriptional effects of Ermin deficiency across age and sex. We observed altered expression of transcription factors at early ages, and in protein processing and synaptic function over time. In silico gene perturbation and ChIP-seq analysis were used to elucidate the roles that differentially expressed transcription factors play in oligodendrocyte differentiation and as well as in their effects on protein processing and synaptic function. Finally, we assessed the relationship between early molecular changes in Ermin deficiency in neurological conditions using genome-wide association studies. Our observations suggest that there are common mechanisms between Ermin deficiency and biological processes influenced by genetic variants of genetic generalised epilepsy. Our findings demonstrate that in the Ermin-deficient model of abnormal myelination, early changes in transcription factor expression are associated with dysregulation in oligodendrocyte differentiation, synaptic organisation, and protein modification. These transcriptional changes are also enriched for genetic variants in neurological disease and provide insight into the early molecular mechanisms involving abnormal myelination in neurological disorders. Submitted/Accepted version 2024-03-25T07:25:19Z 2024-03-25T07:25:19Z 2024 Conference Paper Oh, S. L., Ziaei, A., Tan, L. J., Utami, K. H., Pouladi, M. A. & Langley, S. R. (2024). Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency. 2024 Myelin Gordon Research Conference (GRC). https://hdl.handle.net/10356/173229 https://www.grc.org/myelin-conference/2024/ en © 2024 Gordon Research Conferences. All rights reserved. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Neurological disorders Ermin deficiency Oh, Sher Li Ziaei, Amin Tan, Liang Juin Utami, Kagistia Hana Pouladi, Mahmoud A. Langley, Sarah Raye Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency |
| title | Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency |
| title_full | Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency |
| title_fullStr | Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency |
| title_full_unstemmed | Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency |
| title_short | Understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising Ermin deficiency |
| title_sort | understanding early molecular mechanisms of abnormal myelination in neurological conditions by characterising ermin deficiency |
| topic | Medicine, Health and Life Sciences Neurological disorders Ermin deficiency |
| url | https://hdl.handle.net/10356/173229 https://www.grc.org/myelin-conference/2024/ |
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