Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease
Huiqin Zhou,1– 3,* Yunjia Peng,2,3,* Xinhua Huo,2,3 Bingqing Li,2,3 Huasheng Liu,4 Jian Wang,3,5 Gaihua Zhang1 1College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China; 2Hunan Guangxiu Hospital, Hunan Normal University, Changsha, People’s Republic of C...
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Dove Medical Press
2025-02-01
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| author | Zhou H Peng Y Huo X Li B Liu H Wang J Zhang G |
| author_facet | Zhou H Peng Y Huo X Li B Liu H Wang J Zhang G |
| author_sort | Zhou H |
| collection | DOAJ |
| description | Huiqin Zhou,1– 3,* Yunjia Peng,2,3,* Xinhua Huo,2,3 Bingqing Li,2,3 Huasheng Liu,4 Jian Wang,3,5 Gaihua Zhang1 1College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China; 2Hunan Guangxiu Hospital, Hunan Normal University, Changsha, People’s Republic of China; 3National Engineering Center of Human Stem Cell, Changsha, People’s Republic of China; 4Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5The Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gaihua Zhang, The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China. FuRong Laboratory, Changsha, Hunan, 410078, People’s Republic of China, Email ghzhang@hunnu.edu.cn Jian Wang, The Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410006, People’s Republic of China, Email 205106@csu.edu.cnBackground: Ferroptosis is a form of programmed cell death triggered by iron-dependent lipid peroxidation, characterized by iron accumulation and elevated reactive oxygen species (ROS), leading to cell membrane damage. It is associated with a variety of diseases. However, the cellular and molecular links between ferroptosis, immune inflammation, and the brain-peripheral blood axis in Alzheimer’s disease (AD) remain unclear.Methods: We integrated bulk RNA-seq data from AD brain tissue and peripheral blood and refined the screening of AD candidate genes through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and other approaches. Additionally, we analyzed single-cell RNA-seq (scRNA-seq) data from AD patients’ brain tissue and peripheral blood, combined with scRNA-seq data from experimental autoimmune encephalomyelitis (EAE) mouse brain tissue. This enabled us to explore AD-related molecular mechanisms from a cell-type-specific perspective. Finally, candidate genes were validated in ferroptosis models using reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence methods.Results: Bulk RNA-seq analysis identified SLC11A1, an inflammatory gene associated with AD. Single-cell RNA-seq analysis further revealed that SLC11A1 expression was significantly elevated in the pro-inflammatory (M1-type) microglia and peripheral blood monocytes in AD. Moreover, we identified a microglial subpopulation in AD M1-type microglia that was highly associated with ferroptosis. This subpopulation simultaneously expressed characteristic markers of peripheral blood monocytes, suggesting that these cells may originate from peripheral blood monocytes, thereby triggering neuroinflammation through the ferroptosis pathway. Cell experiments confirmed that SLC11A1 was significantly upregulated in inflammatory microglia induced by ferroptosis.Conclusion: This study reveals the key role of SLC11A1 in AD, particularly in the context of ferroptosis and immune inflammation. It provides a novel molecular mechanistic perspective and offers potential targets for future therapeutic strategies.Keywords: Alzheimer’s disease, single-cell RNA sequencing, microglia, ferroptosis, SLC11A1 |
| format | Article |
| id | doaj-art-b20ff84ac53f4bddb2dd933a023edd4b |
| institution | Kabale University |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj-art-b20ff84ac53f4bddb2dd933a023edd4b2025-02-11T17:30:56ZengDove Medical PressJournal of Inflammation Research1178-70312025-02-01Volume 1821052122100023Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s DiseaseZhou HPeng YHuo XLi BLiu HWang JZhang GHuiqin Zhou,1– 3,* Yunjia Peng,2,3,* Xinhua Huo,2,3 Bingqing Li,2,3 Huasheng Liu,4 Jian Wang,3,5 Gaihua Zhang1 1College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China; 2Hunan Guangxiu Hospital, Hunan Normal University, Changsha, People’s Republic of China; 3National Engineering Center of Human Stem Cell, Changsha, People’s Republic of China; 4Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5The Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gaihua Zhang, The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China. FuRong Laboratory, Changsha, Hunan, 410078, People’s Republic of China, Email ghzhang@hunnu.edu.cn Jian Wang, The Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha, 410006, People’s Republic of China, Email 205106@csu.edu.cnBackground: Ferroptosis is a form of programmed cell death triggered by iron-dependent lipid peroxidation, characterized by iron accumulation and elevated reactive oxygen species (ROS), leading to cell membrane damage. It is associated with a variety of diseases. However, the cellular and molecular links between ferroptosis, immune inflammation, and the brain-peripheral blood axis in Alzheimer’s disease (AD) remain unclear.Methods: We integrated bulk RNA-seq data from AD brain tissue and peripheral blood and refined the screening of AD candidate genes through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and other approaches. Additionally, we analyzed single-cell RNA-seq (scRNA-seq) data from AD patients’ brain tissue and peripheral blood, combined with scRNA-seq data from experimental autoimmune encephalomyelitis (EAE) mouse brain tissue. This enabled us to explore AD-related molecular mechanisms from a cell-type-specific perspective. Finally, candidate genes were validated in ferroptosis models using reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence methods.Results: Bulk RNA-seq analysis identified SLC11A1, an inflammatory gene associated with AD. Single-cell RNA-seq analysis further revealed that SLC11A1 expression was significantly elevated in the pro-inflammatory (M1-type) microglia and peripheral blood monocytes in AD. Moreover, we identified a microglial subpopulation in AD M1-type microglia that was highly associated with ferroptosis. This subpopulation simultaneously expressed characteristic markers of peripheral blood monocytes, suggesting that these cells may originate from peripheral blood monocytes, thereby triggering neuroinflammation through the ferroptosis pathway. Cell experiments confirmed that SLC11A1 was significantly upregulated in inflammatory microglia induced by ferroptosis.Conclusion: This study reveals the key role of SLC11A1 in AD, particularly in the context of ferroptosis and immune inflammation. It provides a novel molecular mechanistic perspective and offers potential targets for future therapeutic strategies.Keywords: Alzheimer’s disease, single-cell RNA sequencing, microglia, ferroptosis, SLC11A1https://www.dovepress.com/integrating-bulk-and-single-cell-transcriptomic-data-to-identify-ferro-peer-reviewed-fulltext-article-JIRalzheimer's diseasesingle-cell rna sequencingmicrogliaferroptosisslc11a1 |
| spellingShingle | Zhou H Peng Y Huo X Li B Liu H Wang J Zhang G Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease Journal of Inflammation Research alzheimer's disease single-cell rna sequencing microglia ferroptosis slc11a1 |
| title | Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease |
| title_full | Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease |
| title_fullStr | Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease |
| title_full_unstemmed | Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease |
| title_short | Integrating Bulk and Single-Cell Transcriptomic Data to Identify Ferroptosis-Associated Inflammatory Gene in Alzheimer’s Disease |
| title_sort | integrating bulk and single cell transcriptomic data to identify ferroptosis associated inflammatory gene in alzheimer rsquo s disease |
| topic | alzheimer's disease single-cell rna sequencing microglia ferroptosis slc11a1 |
| url | https://www.dovepress.com/integrating-bulk-and-single-cell-transcriptomic-data-to-identify-ferro-peer-reviewed-fulltext-article-JIR |
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