Systematic Analysis of Actively Transcribed Core Matrisome Genes Across Tissues and Cell Phenotypes

Tellman, Tristen V.; Dede, Merve; Aggarwal, Vikram A; Salmon, D. Michael; Naba, Alexandra; Farach-Carson, Mary C.

doi:10.1016/j.matbio.2022.06.003

Cited by 11 publications

(6 citation statements)

References 57 publications

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“…In both species, we found the strongest transcriptome alterations in FB clusters, specifically in genes of the so-called matrisome, which includes collagens, proteoglycans, glycoproteins, and ECM regulators [22][23][24]. The matrisome, which was recently defined for large-scale in silico analyses, provides a comprehensive overview of the components of the ECM [51,70,71]. Although several characteristics of ECM alterations in (hypertrophic) scars have already been described [72], our study provides the first large dataset analyzing changes in the entire matrisome in mice and humans during wound healing and scar formation.…”

Section: Discussionmentioning

confidence: 88%

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring

et al. 2023

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Hypertrophic scars can cause pain, movement restrictions, and reduction in the quality of life. Despite numerous options to treat hypertrophic scarring, efficient therapies are still scarce, and cellular mechanisms are not well understood. Factors secreted by peripheral blood mononuclear cells (PBMCsec) have been previously described for their beneficial effects on tissue regeneration. In this study, we investigated the effects of PBMCsec on skin scarring in mouse models and human scar explant cultures at single-cell resolution (scRNAseq). Mouse wounds and scars, and human mature scars were treated with PBMCsec intradermally and topically. The topical and intradermal application of PBMCsec regulated the expression of various genes involved in pro-fibrotic processes and tissue remodeling. We identified elastin as a common linchpin of anti-fibrotic action in both mouse and human scars. In vitro, we found that PBMCsec prevents TGFβ-mediated myofibroblast differentiation and attenuates abundant elastin expression with non-canonical signaling inhibition. Furthermore, the TGFβ-induced breakdown of elastic fibers was strongly inhibited by the addition of PBMCsec. In conclusion, we conducted an extensive study with multiple experimental approaches and ample scRNAseq data demonstrating the anti-fibrotic effect of PBMCsec on cutaneous scars in mouse and human experimental settings. These findings point at PBMCsec as a novel therapeutic option to treat skin scarring.

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Section: Discussionmentioning

confidence: 88%

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring

et al. 2023

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“…The ECM is also a significant component of the tumor microenvironment. By providing cancer stem cell niches and regulating tumor cell growth, the ECM controls cell signaling essential to maintain tumor tissue ( 51 , 52 ). Tumor progression causes ECM remodeling, leading to the interaction between reconstructed ECM and tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids

Song,

Jiang,

et al. 2024

Sci. Adv.

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Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase–AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.

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“…4B). Analyzed across the THBS1, IGFBP4, CYR61 and Emilin1; components of the M17 signature, all are highly transcribed in vascular tissues 82 . The enrichment of a prognostic ECMsignature expression in pericyte niches within recurrent GBM tumors has also been reported in a recent study 83 .…”

Section: Discussionmentioning

confidence: 99%

A prognostic matrix gene expression signature defines functional glioblastoma phenotypes and niches

Vishnoi,

Dereli,

Yin

et al. 2024

Preprint

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Background. Interactions among tumor, immune, and vascular niches play major roles in driving glioblastoma (GBM) malignancy and treatment responses. The composition, heterogeneity, and localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. Methods. Here, through computational genomics and proteomics approaches, we analyzed the functional and clinical relevance of CMP expression in GBM at bulk, single cell, and spatial anatomical resolution. Results. We identified genes encoding CMPs whose expression levels categorize GBM tumors into CMP expression-high (M-H) and CMP expression-low (M-L) groups. CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, infiltration of pro-tumor immune cells, and immune checkpoint gene expression. Anatomical and single-cell transcriptome analyses indicate that matrisome gene expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells driving GBM progression. Finally, we identified a 17-gene CMP expression signature, termed Matrisome 17 (M17) signature that further refines the prognostic value of CMP genes. The M17 signature is a significantly stronger prognostic factor compared to MGMT promoter methylation status as well as canonical subtypes, and importantly, potentially predicts responses to PD1 blockade. Conclusion. The matrisome gene expression signature provides a robust stratification of GBM patients by survival and potential biomarkers of functionally relevant GBM niches that can mediate mesenchymal-immune cross talk. Patient stratification based on matrisome profiles can contribute to selection and optimization of treatment strategies.

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Systematic Analysis of Actively Transcribed Core Matrisome Genes Across Tissues and Cell Phenotypes

Cited by 11 publications

References 57 publications

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring

The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring

Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids

A prognostic matrix gene expression signature defines functional glioblastoma phenotypes and niches

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