Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia
Background: Maternal diabetes alters gene expression leading to neural tube defects (NTDs) in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs) to high glucose/hyperglycemia results in act...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2014
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| Online Access: | https://hdl.handle.net/10356/101283 http://hdl.handle.net/10220/18417 |
| _version_ | 1811683025696587776 |
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| author | Shyamasundar, Sukanya Bay, Boon Huat Tay, Samuel Sam Wah Kumar, S. Dinesh Rangasamy, Danny Dheen, S. Thameem Jadhav, Shweta P. |
| author2 | Pant, Aditya Bhushan |
| author_facet | Pant, Aditya Bhushan Shyamasundar, Sukanya Bay, Boon Huat Tay, Samuel Sam Wah Kumar, S. Dinesh Rangasamy, Danny Dheen, S. Thameem Jadhav, Shweta P. |
| author_sort | Shyamasundar, Sukanya |
| collection | NTU |
| description | Background: Maternal diabetes alters gene expression leading to neural tube defects (NTDs) in the developing brain. The
mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural
stem cells (NSCs) to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development.
Methods and Findings: NSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and
cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin
reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation) and global DNA
methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin) and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1) proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p) predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers.
Conclusion/ nterpretation: This study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy. |
| first_indexed | 2024-10-01T04:06:11Z |
| format | Journal Article |
| id | ntu-10356/101283 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:06:11Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1012832022-02-16T16:28:34Z Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia Shyamasundar, Sukanya Bay, Boon Huat Tay, Samuel Sam Wah Kumar, S. Dinesh Rangasamy, Danny Dheen, S. Thameem Jadhav, Shweta P. Pant, Aditya Bhushan Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Medicine Background: Maternal diabetes alters gene expression leading to neural tube defects (NTDs) in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs) to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development. Methods and Findings: NSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation) and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin) and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1) proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p) predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers. Conclusion/ nterpretation: This study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy. Published version 2014-01-08T01:46:31Z 2019-12-06T20:36:04Z 2014-01-08T01:46:31Z 2019-12-06T20:36:04Z 2013 2013 Journal Article Shyamasundar, S., Jadhav, S. P., Bay, B. H., Tay, S. S. W., Kumar, S. D., Rangasamy, D., et al. (2013). Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia. PLoS ONE, 8(6), e65945-. 1932-6203 https://hdl.handle.net/10356/101283 http://hdl.handle.net/10220/18417 10.1371/journal.pone.0065945 23776576 en PLoS ONE © 2013 The Authors. This paper was published in PLoS ONE and is made available as an electronic reprint (preprint) with permission of the authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1371/journal.pone.0065945]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf |
| spellingShingle | DRNTU::Science::Medicine Shyamasundar, Sukanya Bay, Boon Huat Tay, Samuel Sam Wah Kumar, S. Dinesh Rangasamy, Danny Dheen, S. Thameem Jadhav, Shweta P. Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| title | Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| title_full | Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| title_fullStr | Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| title_full_unstemmed | Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| title_short | Analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| title_sort | analysis of epigenetic factors in mouse embryonic neural stem cells exposed to hyperglycemia |
| topic | DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/101283 http://hdl.handle.net/10220/18417 |
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