REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells
Down syndrome (DS) is the most frequently diagnosed chromosomal disorder of chromosome 21 (HSA21) aneuploidy, characterized by intellectual disability and reduced lifespan. The transcription repressor, Repressor Element-1 Silencing Transcription factor (REST), which acts as an epigenetic regulator,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Multidisciplinary Digital Publishing Institute
2023
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/109464/1/ijms-24-09980.pdf |
| _version_ | 1824452240197287936 |
|---|---|
| author | Huang, Tan Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa |
| author_facet | Huang, Tan Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa |
| author_sort | Huang, Tan |
| collection | UPM |
| description | Down syndrome (DS) is the most frequently diagnosed chromosomal disorder of chromosome 21 (HSA21) aneuploidy, characterized by intellectual disability and reduced lifespan. The transcription repressor, Repressor Element-1 Silencing Transcription factor (REST), which acts as an epigenetic regulator, is a crucial regulator of neuronal and glial gene expression. In this study, we identified and investigated the role of REST-target genes in human brain tissues, cerebral organoids, and neural cells in Down syndrome. Gene expression datasets generated from healthy controls and DS samples of human brain tissues, cerebral organoids, NPC, neurons, and astrocytes were retrieved from the Gene Ontology (GEO) and Sequence Read Archive (SRA) databases. Differential expression analysis was performed on all datasets to produce differential expression genes (DEGs) between DS and control groups. REST-targeted DEGs were subjected to functional ontologies, pathways, and network analyses. We found that REST-targeted DEGs in DS were enriched for the JAK–STAT and HIF-1 signaling pathways across multiple distinct brain regions, ages, and neural cell types. We also identified REST-targeted DEGs involved in nervous system development, cell differentiation, fatty acid metabolism and inflammation in the DS brain. Based on the findings, we propose REST as the critical regulator and a promising therapeutic target to modulate homeostatic gene expression in the DS brain. |
| first_indexed | 2025-02-19T02:47:22Z |
| format | Article |
| id | upm.eprints-109464 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2025-02-19T02:47:22Z |
| publishDate | 2023 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | upm.eprints-1094642024-12-10T03:24:13Z http://psasir.upm.edu.my/id/eprint/109464/ REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells Huang, Tan Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa Down syndrome (DS) is the most frequently diagnosed chromosomal disorder of chromosome 21 (HSA21) aneuploidy, characterized by intellectual disability and reduced lifespan. The transcription repressor, Repressor Element-1 Silencing Transcription factor (REST), which acts as an epigenetic regulator, is a crucial regulator of neuronal and glial gene expression. In this study, we identified and investigated the role of REST-target genes in human brain tissues, cerebral organoids, and neural cells in Down syndrome. Gene expression datasets generated from healthy controls and DS samples of human brain tissues, cerebral organoids, NPC, neurons, and astrocytes were retrieved from the Gene Ontology (GEO) and Sequence Read Archive (SRA) databases. Differential expression analysis was performed on all datasets to produce differential expression genes (DEGs) between DS and control groups. REST-targeted DEGs were subjected to functional ontologies, pathways, and network analyses. We found that REST-targeted DEGs in DS were enriched for the JAK–STAT and HIF-1 signaling pathways across multiple distinct brain regions, ages, and neural cell types. We also identified REST-targeted DEGs involved in nervous system development, cell differentiation, fatty acid metabolism and inflammation in the DS brain. Based on the findings, we propose REST as the critical regulator and a promising therapeutic target to modulate homeostatic gene expression in the DS brain. Multidisciplinary Digital Publishing Institute 2023-06-10 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/109464/1/ijms-24-09980.pdf Huang, Tan and Fakurazi, Sharida and Cheah, Pike-See and Ling, King-Hwa (2023) REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells. International Journal of Molecular Sciences, 24 (12). pp. 1-19. ISSN 1422-0067 https://www.mdpi.com/1422-0067/24/12/9980 10.3390/ijms24129980 |
| spellingShingle | Huang, Tan Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells |
| title | REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells |
| title_full | REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells |
| title_fullStr | REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells |
| title_full_unstemmed | REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells |
| title_short | REST targets JAK–STAT and HIF-1 signaling pathways in human Down syndrome brain and neural cells |
| title_sort | rest targets jak stat and hif 1 signaling pathways in human down syndrome brain and neural cells |
| url | http://psasir.upm.edu.my/id/eprint/109464/1/ijms-24-09980.pdf |
| work_keys_str_mv | AT huangtan resttargetsjakstatandhif1signalingpathwaysinhumandownsyndromebrainandneuralcells AT fakurazisharida resttargetsjakstatandhif1signalingpathwaysinhumandownsyndromebrainandneuralcells AT cheahpikesee resttargetsjakstatandhif1signalingpathwaysinhumandownsyndromebrainandneuralcells AT lingkinghwa resttargetsjakstatandhif1signalingpathwaysinhumandownsyndromebrainandneuralcells |