Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction
Diabetes-associated cognitive decline (DCD), is one of the complications of diabetes, which is characterized by a series of neurophysiological and pathological abnormalities. However, the exact pathogenesis of DCD is still unknown. Single-cell RNA sequencing (scRNA-seq) could discover unusual subpop...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.891039/full |
| _version_ | 1811232225810710528 |
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| author | Shizhan Ma Wenkai Bi Xueying Liu Shangbin Li Yaxin Qiu Chengcheng Huang Renjun Lv Qingqing Yin |
| author_facet | Shizhan Ma Wenkai Bi Xueying Liu Shangbin Li Yaxin Qiu Chengcheng Huang Renjun Lv Qingqing Yin |
| author_sort | Shizhan Ma |
| collection | DOAJ |
| description | Diabetes-associated cognitive decline (DCD), is one of the complications of diabetes, which is characterized by a series of neurophysiological and pathological abnormalities. However, the exact pathogenesis of DCD is still unknown. Single-cell RNA sequencing (scRNA-seq) could discover unusual subpopulations, explore functional heterogeneity and identify signaling pathways and potential markers. The aim of this research was to provide deeper opinion into molecular and cellular changes underlying DCD, identify different cellular types of the diabetic mice hippocampus at single-cell level, and elucidate the factors mediating the pathogenesis of DCD. To elucidate cell specific gene expression changes in the hippocampus of diabetic encephalopathy. Single-cell RNA sequencing of hippocampus from db/m and db/db mice was carried out. Subclustering analysis was performed to further describe microglial cell subpopulations. Interestingly using immunohistochemistry, these findings were confirmed at the protein level. Single cell analysis yielded transcriptome data for 14621 hippocampal cells and defined 11 different cell types. Analysis of differentially expressed genes in the microglia compartments indicated that infection- and immune system process- associated terms, oxidative stress and inflammation play vital roles in the progression of DCD. Compared with db/m mouse, experiments at the protein level supported the activation of microglia, increased expression of inflammatory factors and oxidative stress damage in the hippocampus of db/db mouse. In addition, a major finding of our research was the subpopulation of microglia that express genes related to pro-inflammatory disease-associated microglia (DAM). Our research reveals pathological alterations of inflammation and oxidative stress mediated hippocampal damage in the db/db mice, and may provide potential diagnostic biomarkers and therapeutic interventions for DCD. |
| first_indexed | 2024-04-12T11:00:05Z |
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| id | doaj.art-352549c1b659453b9bf13ef4f14cb41f |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T11:00:05Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-352549c1b659453b9bf13ef4f14cb41f2022-12-22T03:35:59ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.891039891039Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive DysfunctionShizhan Ma0Wenkai Bi1Xueying Liu2Shangbin Li3Yaxin Qiu4Chengcheng Huang5Renjun Lv6Qingqing Yin7Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaClinical Education Administration, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDiabetes-associated cognitive decline (DCD), is one of the complications of diabetes, which is characterized by a series of neurophysiological and pathological abnormalities. However, the exact pathogenesis of DCD is still unknown. Single-cell RNA sequencing (scRNA-seq) could discover unusual subpopulations, explore functional heterogeneity and identify signaling pathways and potential markers. The aim of this research was to provide deeper opinion into molecular and cellular changes underlying DCD, identify different cellular types of the diabetic mice hippocampus at single-cell level, and elucidate the factors mediating the pathogenesis of DCD. To elucidate cell specific gene expression changes in the hippocampus of diabetic encephalopathy. Single-cell RNA sequencing of hippocampus from db/m and db/db mice was carried out. Subclustering analysis was performed to further describe microglial cell subpopulations. Interestingly using immunohistochemistry, these findings were confirmed at the protein level. Single cell analysis yielded transcriptome data for 14621 hippocampal cells and defined 11 different cell types. Analysis of differentially expressed genes in the microglia compartments indicated that infection- and immune system process- associated terms, oxidative stress and inflammation play vital roles in the progression of DCD. Compared with db/m mouse, experiments at the protein level supported the activation of microglia, increased expression of inflammatory factors and oxidative stress damage in the hippocampus of db/db mouse. In addition, a major finding of our research was the subpopulation of microglia that express genes related to pro-inflammatory disease-associated microglia (DAM). Our research reveals pathological alterations of inflammation and oxidative stress mediated hippocampal damage in the db/db mice, and may provide potential diagnostic biomarkers and therapeutic interventions for DCD.https://www.frontiersin.org/articles/10.3389/fendo.2022.891039/fulldiabetes-associated cognitive dysfunctionhippocampusmicrogliainflammationsingle-cell transcriptomics |
| spellingShingle | Shizhan Ma Wenkai Bi Xueying Liu Shangbin Li Yaxin Qiu Chengcheng Huang Renjun Lv Qingqing Yin Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction Frontiers in Endocrinology diabetes-associated cognitive dysfunction hippocampus microglia inflammation single-cell transcriptomics |
| title | Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction |
| title_full | Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction |
| title_fullStr | Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction |
| title_full_unstemmed | Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction |
| title_short | Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction |
| title_sort | single cell sequencing analysis of the db db mouse hippocampus reveals cell type specific insights into the pathobiology of diabetes associated cognitive dysfunction |
| topic | diabetes-associated cognitive dysfunction hippocampus microglia inflammation single-cell transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.891039/full |
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