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Deciphering the age-dependent changes of pulmonary fibroblasts in mice by single-cell transcriptomics

ABSTRACT: In brief, lung resident cells were isolated from lung of mice and 10x Genomics single cell RNAseq was applied to identify distinct cell populations. Low quality cells and outliers were discarded, and only ～22,826 viable cells were used for downstream analysis. These included ~5,237 cells – NB(10days mice); ~4,804 cells – Adult-M(2months mice); ~6,561cells-SD-10M (10month mice) ; ~6,224cells-SD-1d5Y (18month mice). Unsupervised clustering and gene expression were visualized with the Seurat 2.0 on R studio, and assignment of cell clusters was based on expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Overall, we found that a specific lung fibroblast population, We present a single-cell transcriptomic atlas encompassing lung tissues derived from mice at various stages of aging, uncovering substantial shifts in fibroblast differentiation and immune regulation throughout the aging process.

ORGANISM(S): Mus musculus

PROVIDER: GSE237757 | GEO | 2023/11/21

REPOSITORIES: GEO

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Dynamic interplay between IL1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration

Project description:In brief, skin resident cells were isolated from dorsal skin of mice and 10x Genomics single cell RNAseq was applied to identify distinct cell populations. Low quality cells and outliers were discarded, and only ～24,409 viable cells were used for downstream analysis. Unsupervised clustering and gene expression were visualized with the Seurat 2.0 on R studio, and assignment of cell clusters was based on expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Overall, we found that a specific dermal fibroblast population, with high DPP4, Sca1 and WNT2 expression, has robust capacity for adipocyte differentiation and acts key role in maintaining dermis homeostasis.

2023-06-10 | GSE189241 | GEO

Dynamic interplay between IL1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration

Project description:Cells were isolated from wounded skin tissue and administered into single cell RNA transcriptome sequencing to deconstruct cell hierarchy of dermal fibroblast population and underlying regulating mechanisms. In brief, 7~9 weeks old male C57BL/6 mice were anesthetized and one full-thickness wound (1.0 cm x 0.5 cm in size) was generated on shaved dorsal skin. Animals were sacrificed at indicated intervals after and wound bed tissues were collected for cell isolation and subsequent 10x Genomics single cell RNAseq. Sequencing was performed on Illumina Novaseq6000 platform (Illumina). The generated raw gene expression matrix was converted into Seurat objects using the R package Seurat v3.0. After low quality cells and outliers were discarded, 10233 cells from non-lesional skin, 7807 cells from wound beds at post-wounding day 2 (PWD2), and 4925 cells from wound tissue at PWD7 were used for downstream analysis. Next, unsupervised clustering and gene expression were visualized with the Seurat 3.0 on R studio, and assignment and identification of cell clusters was based on the expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Together, our study has identified a specific dermal fibroblast population with high DPP4, Sca1 and WNT2 expression, which is committed into adipocyte upon wounding, and define the differentiation trajectory of this adipocyte precursor during skin regeneration.

2023-06-10 | GSE196800 | GEO

The Influence of Sleep Deprivation on Hippocampal CA1 Gene Expression: Relation to Stress and Aging

Project description:Sleep deprivation (SD) in young adults is associated with metabolic, stress and cognitive responses that are also characteristic of brain aging. Given that sleep architecture changes with age, including increased fragmentation and decreased slow wave activity, it seems reasonable to investigate potential molecular relationships between SD and aging in brain tissue. Here, we tested the hypothesis that young rats exposed to 24 or 72 hour SD would respond with stress and aging-like shifts in brain hippocampal CA1 gene expression. SD animals showed blood corticosterone and weight changes consistent with a stress response. Microarray results, validated by Western blot and comparison to prior SD studies, pointed to disruptions in neurotransmission, sleep pressure signaling, and macromolecular synthesis. In a separate experiment, animals exposed to 24 or 72 hour novel environment stress recapitulated nearly one third of the SD transcriptional profile, particularly upregulated apoptotic and immune signaling pathways. Compared to aging (based on three previously published independent hippocampal aging studies), SD transcriptional profiles agreed for neurogenesis and energy pathways. However, immune signaling, glial activity, macromolecular synthesis and neuronal function all showed an SD profile that was, at least in part, opposed by aging. We conclude that while stress and SD have discrete molecular signatures, they do show a subset of highly similar changes. However, the same could not be said of aging and SD, where a similar subset of genes is changed, but in partially divergent directions. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel targets for future SD-countering therapeutics.

2012-07-17 | GSE34424 | GEO

Single-cell transcriptional profiles of lung CD45+ immune cells from WT and Ptgs2-cKO mice

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2022-07-19 | GSE206449 | GEO

RNA-seq of lung myeloid cells from WT and Ptgs2-cKO mice

Project description:To investigate the role of the COX-2-dependent lung fibroblast program in reprogramming lung myeloid cells, we generated fibroblast-targeted Ptgs2 conditional knockout mice by crossing Pdgfra-Cre mice with Ptgs2flox/flox mice. Then we isolated two primary types of lung resident DCs-CD103+ conventional DC (cDC1) and CD11b+ conventional DC (cDC2), and lung monocytes from WT and Ptgs2 cKO mice by fluorescence-activated cell sorting and performed RNA sequencing.

2022-07-19 | E-MTAB-11888 | biostudies-arrayexpress

Metformin improves cognition of aged mice by promoting cerebral angiogenesis and neurogenesis [blood]

Project description:We implemented transcriptomic analyses of blood of 8-10M mice; These mice with the treatment of metformin for 30 days.

2020-09-23 | GSE140715 | GEO

GDF11 rejuvenates neural stem cells via Smad2/3-PI3K-AKT-mTOR and reverses aged-dependent cognitive decline [mice tissue]

Project description:We implemented transcriptomic analyses of different tissues of 10M and 15M mice; These mice with the treatment of rGDF11 for 30 days.

2022-12-31 | GSE142759 | GEO

An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

Project description:Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. We used single cell transcriptomics and mass spectrometry to quantify changes in cellular activity states of 30 cell types and the tissue proteome from lungs of young and old mice. Aging led to increased transcriptional noise, indicating deregulated epigenetic control. We observed highly distinct effects of aging on cell type level, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts as a novel hallmark of lung aging. Proteomic profiling revealed extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and Collagen XIV. Computational integration of the aging proteome and single cell transcriptomes predicted the cellular source of regulated proteins and created a first unbiased reference of the aging lung. The lung aging atlas can be accessed via an interactive user-friendly webtool at: https://theislab.github.io/LungAgingAtlas

2019-01-21 | PXD012307 | Pride

Single cell atlas of the aging mouse trachea

Project description:The airways conduct gases to and from the gas-exchanging alveoli of the lung and are the site of age-related diseases, such as chronic obstructive pulmonary disease, asthma, and bronchogenic carcinoma. Here we set out to study the effects of aging on the cellular composition and gene expression of murine airway. We present a comprehensive single-cell RNA-sequencing atlas of tracheas from young (2 month) and aged (24 month) mice, comprising diverse populations of cells, including epithelial, endothelial, immune, fibroblast, and cartilage cells.

2024-03-05 | GSE244215 | GEO

scRNA-seq of lung CD140a+ mesenchymal cells (fibroblasts) from CD140a-EGFP reporter mice

Project description:To investigate the heterogeneity of lung CD140a+ mesenchymal cells (fibroblasts) and identify the specific lung fibroblast subset, we purified CD140a+ lung cells using CD140a-EGFP reporter mice for a higher-resolution scRNA-seq.

2022-07-19 | E-MTAB-11875 | biostudies-arrayexpress

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