Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus
IntroductionType 2 diabetes mellitus (T2DM) is a disease that involves autoimmunity. However, how immune cells function in the peripheral blood remains unclear. Exploring T2DM biomarkers via single-cell RNA sequencing (scRNA-seq) could provide new insights into the underlying molecular mechanisms.Me...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1501660/full |
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| author | Jindong Zhao Jindong Zhao Jindong Zhao Zhaohui Fang Zhaohui Fang Zhaohui Fang |
| author_facet | Jindong Zhao Jindong Zhao Jindong Zhao Zhaohui Fang Zhaohui Fang Zhaohui Fang |
| author_sort | Jindong Zhao |
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| description | IntroductionType 2 diabetes mellitus (T2DM) is a disease that involves autoimmunity. However, how immune cells function in the peripheral blood remains unclear. Exploring T2DM biomarkers via single-cell RNA sequencing (scRNA-seq) could provide new insights into the underlying molecular mechanisms.MethodsThe clinical trial registration number is ChiCTR2100049613. In this study, we included three healthy participants and three T2DM patients. The observed clinical indicators included weight and fasting blood glucose (FBG), glycosylated haemoglobin A1c (HbA1c) and fasting insulin levels. Direct separation and purification of peripheral blood mononuclear cells (PBMCs) were performed via the Ficoll density gradient centrifugation method. Immune cell types were identified via scRNA-seq. The differentially expressed genes, biological functions, cell cycle dynamics, and correlations between blood glucose indicators and genes in different cell types were analysed.ResultsThere were differences between the healthy and T2DM groups in terms of FBG and HbA1c (p<0.05 or p<0.01). We profiled 13,591 cells and 3188 marker genes from PBMCs. B cells, T cells, monocytes, and NK cells were grouped into 4 subclusters from PBMCs. CD4+ T cells are mainly in the memory activation stage, and CD8+ T cells are effectors. Monocytes include mainly CD14+ monocytes and FCGR3A+ monocytes. There were 119 differentially expressed genes in T cells and 175 differentially expressed genes in monocytes. Gene set enrichment analysis revealed that the marker genes were enriched in HALLMARK_ INTERFERON_GAMMA_RESPONSE and HALLMARK_TNFA_SIGNALING_VIA_ NFKB. Moreover, TNFRSF1A was identified as the core gene involved in network interactions in T cells.DiscussionOur study provides a transcriptional map of immune cells from PBMCs and provides a framework for understanding the immune status and potential immune mechanisms of T2DM patients via scRNA-seq.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2100049613. |
| format | Article |
| id | doaj-art-f78a3b46ebb4496ab3531f967e0b2ebe |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-f78a3b46ebb4496ab3531f967e0b2ebe2025-01-23T05:10:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15016601501660Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitusJindong Zhao0Jindong Zhao1Jindong Zhao2Zhaohui Fang3Zhaohui Fang4Zhaohui Fang5Department of Endocrinology Two, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaCenter for Xin’an Medicine and Modernization of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDiabetes Institute, Anhui Academy Chinese Medicine, Hefei, ChinaDepartment of Endocrinology Two, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaCenter for Xin’an Medicine and Modernization of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, ChinaDiabetes Institute, Anhui Academy Chinese Medicine, Hefei, ChinaIntroductionType 2 diabetes mellitus (T2DM) is a disease that involves autoimmunity. However, how immune cells function in the peripheral blood remains unclear. Exploring T2DM biomarkers via single-cell RNA sequencing (scRNA-seq) could provide new insights into the underlying molecular mechanisms.MethodsThe clinical trial registration number is ChiCTR2100049613. In this study, we included three healthy participants and three T2DM patients. The observed clinical indicators included weight and fasting blood glucose (FBG), glycosylated haemoglobin A1c (HbA1c) and fasting insulin levels. Direct separation and purification of peripheral blood mononuclear cells (PBMCs) were performed via the Ficoll density gradient centrifugation method. Immune cell types were identified via scRNA-seq. The differentially expressed genes, biological functions, cell cycle dynamics, and correlations between blood glucose indicators and genes in different cell types were analysed.ResultsThere were differences between the healthy and T2DM groups in terms of FBG and HbA1c (p<0.05 or p<0.01). We profiled 13,591 cells and 3188 marker genes from PBMCs. B cells, T cells, monocytes, and NK cells were grouped into 4 subclusters from PBMCs. CD4+ T cells are mainly in the memory activation stage, and CD8+ T cells are effectors. Monocytes include mainly CD14+ monocytes and FCGR3A+ monocytes. There were 119 differentially expressed genes in T cells and 175 differentially expressed genes in monocytes. Gene set enrichment analysis revealed that the marker genes were enriched in HALLMARK_ INTERFERON_GAMMA_RESPONSE and HALLMARK_TNFA_SIGNALING_VIA_ NFKB. Moreover, TNFRSF1A was identified as the core gene involved in network interactions in T cells.DiscussionOur study provides a transcriptional map of immune cells from PBMCs and provides a framework for understanding the immune status and potential immune mechanisms of T2DM patients via scRNA-seq.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2100049613.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1501660/fulltype 2 diabetes mellitusperipheral blood mononuclear cellssingle-cell RNA sequencingT cellsmonocytes |
| spellingShingle | Jindong Zhao Jindong Zhao Jindong Zhao Zhaohui Fang Zhaohui Fang Zhaohui Fang Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus Frontiers in Immunology type 2 diabetes mellitus peripheral blood mononuclear cells single-cell RNA sequencing T cells monocytes |
| title | Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus |
| title_full | Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus |
| title_fullStr | Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus |
| title_full_unstemmed | Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus |
| title_short | Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus |
| title_sort | single cell rna sequencing reveals the dysfunctional characteristics of pbmcs in patients with type 2 diabetes mellitus |
| topic | type 2 diabetes mellitus peripheral blood mononuclear cells single-cell RNA sequencing T cells monocytes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1501660/full |
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