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Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing
BACKGROUND: Hip fractures in the elderly have significant consequences, stemming from the initial trauma and subsequent surgeries. Hidden blood loss and stress due to concealed injury sites could impact the whole osteoimmune microenvironment. This study employs scRNA-seq technique to map immune prof...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580557/ https://www.ncbi.nlm.nih.gov/pubmed/37848979 http://dx.doi.org/10.1186/s12979-023-00380-6 |
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author | Lu, Yining Luo, Yang Zhang, Qi Chen, Wei Zhang, Ning Wang, Ling Zhang, Yingze |
author_facet | Lu, Yining Luo, Yang Zhang, Qi Chen, Wei Zhang, Ning Wang, Ling Zhang, Yingze |
author_sort | Lu, Yining |
collection | PubMed |
description | BACKGROUND: Hip fractures in the elderly have significant consequences, stemming from the initial trauma and subsequent surgeries. Hidden blood loss and stress due to concealed injury sites could impact the whole osteoimmune microenvironment. This study employs scRNA-seq technique to map immune profiles in elderly hip fracture patients from post-trauma to the recovery period, investigating the dynamic changes of immune inflammation regulation subgroups. METHODS: We collected peripheral blood samples from four elderly hip fracture patients (two males and two females, all > 75 years of age) at three different time points (24 h post-trauma, 24 h post-operation, and day 7 post-operation) and applied scRNA-seq technique to analyze the cellular heterogeneity and identify differentially expressed genes in peripheral blood individual immune cells from elderly hip fracture patients. RESULTS: In this study, we analyzed the composition and gene expression profiles of peripheral blood mononuclear cells (PBMCs) from elderly hip fracture patients by scRNA-seq and further identified new CD14 monocyte subpopulations based on marker genes and transcriptional profiles. Distinct gene expression changes were observed in various cell subpopulations at different time points. C-Mono2 monocyte mitochondria-related genes were up-regulated and interferon-related and chemokine-related genes were down-regulated within 24 h post-operation. Further analysis of gene expression profiles at day 7 post-operation showed that C-Mono2 monocytes showed downregulation of inflammation-related genes and osteoblast differentiation-related genes. However, the expression of these genes in cytotoxic T cells, Treg cells, and B cell subsets exhibited a contrasting trend. GZMK(+)CD8(+) cytotoxic T cells showed downregulation of chemokine-related genes, and Treg cells showed upregulation of genes related to the JAK/STAT signaling pathway. Furthermore, we examined interactions among diverse immune cell subsets, pinpointing specific ligand-receptor pairs. These findings imply cross-talk and communication between various cell types in the post-traumatic immune response. CONCLUSIONS: Our study elucidates the notable alterations in immune cell subpopulations during different stages of hip fracture in elderly patients, both in terms of proportions and differential gene expressions. These changes provide significant clinical implications for tissue repair, infection prevention, and fracture healing in clinic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-023-00380-6. |
format | Online Article Text |
id | pubmed-10580557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105805572023-10-18 Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing Lu, Yining Luo, Yang Zhang, Qi Chen, Wei Zhang, Ning Wang, Ling Zhang, Yingze Immun Ageing Research BACKGROUND: Hip fractures in the elderly have significant consequences, stemming from the initial trauma and subsequent surgeries. Hidden blood loss and stress due to concealed injury sites could impact the whole osteoimmune microenvironment. This study employs scRNA-seq technique to map immune profiles in elderly hip fracture patients from post-trauma to the recovery period, investigating the dynamic changes of immune inflammation regulation subgroups. METHODS: We collected peripheral blood samples from four elderly hip fracture patients (two males and two females, all > 75 years of age) at three different time points (24 h post-trauma, 24 h post-operation, and day 7 post-operation) and applied scRNA-seq technique to analyze the cellular heterogeneity and identify differentially expressed genes in peripheral blood individual immune cells from elderly hip fracture patients. RESULTS: In this study, we analyzed the composition and gene expression profiles of peripheral blood mononuclear cells (PBMCs) from elderly hip fracture patients by scRNA-seq and further identified new CD14 monocyte subpopulations based on marker genes and transcriptional profiles. Distinct gene expression changes were observed in various cell subpopulations at different time points. C-Mono2 monocyte mitochondria-related genes were up-regulated and interferon-related and chemokine-related genes were down-regulated within 24 h post-operation. Further analysis of gene expression profiles at day 7 post-operation showed that C-Mono2 monocytes showed downregulation of inflammation-related genes and osteoblast differentiation-related genes. However, the expression of these genes in cytotoxic T cells, Treg cells, and B cell subsets exhibited a contrasting trend. GZMK(+)CD8(+) cytotoxic T cells showed downregulation of chemokine-related genes, and Treg cells showed upregulation of genes related to the JAK/STAT signaling pathway. Furthermore, we examined interactions among diverse immune cell subsets, pinpointing specific ligand-receptor pairs. These findings imply cross-talk and communication between various cell types in the post-traumatic immune response. CONCLUSIONS: Our study elucidates the notable alterations in immune cell subpopulations during different stages of hip fracture in elderly patients, both in terms of proportions and differential gene expressions. These changes provide significant clinical implications for tissue repair, infection prevention, and fracture healing in clinic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-023-00380-6. BioMed Central 2023-10-17 /pmc/articles/PMC10580557/ /pubmed/37848979 http://dx.doi.org/10.1186/s12979-023-00380-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lu, Yining Luo, Yang Zhang, Qi Chen, Wei Zhang, Ning Wang, Ling Zhang, Yingze Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing |
title | Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing |
title_full | Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing |
title_fullStr | Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing |
title_full_unstemmed | Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing |
title_short | Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing |
title_sort | decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell rna sequencing |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580557/ https://www.ncbi.nlm.nih.gov/pubmed/37848979 http://dx.doi.org/10.1186/s12979-023-00380-6 |
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