Skin regeneration is enabled in the absence of fibroblast inflammatory priming
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA713822 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR10820400.fastq.gz | Fastqsanger.gz | |||
| SRR10820401_1.fastq.gz | Fastqsanger.gz | |||
| SRR10820401_2.fastq.gz | Fastqsanger.gz | |||
| SRR10820402.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 145 |
Similar Datasets
Project description:Mammalian skin wounds heal by forming fibrotic scars. We report that reindeer antler velvet exhibits regenerative wound healing, whereas identical injury to back skin forms scar. This regenerative capacity was retained following ectopic transplantation of velvet to scar-forming sites. Single-cell mRNA/ATAC-Sequencing revealed that while uninjured velvet fibroblasts resembled human fetal fibroblasts, back skin fibroblasts were enriched in pro-inflammatory features resembling adult human fibroblasts. Injury elicited site-specific immune polarization; back skin fibroblasts amplified the immune response, whereas velvet fibroblasts adopted an immunosuppressive state leading to restrained myeloid maturation and hastened immune resolution ultimately enabling myofibroblast reversion to a regeneration-competent state. Finally, regeneration was blunted following application of back skin associated immunostimulatory signals or inhibition of pro-regenerative factors secreted exclusive to velvet fibroblasts. This study highlights a unique model to interrogate mechanisms underlying divergent healing outcomes and nominates both decoupling of stromal-immune crosstalk and reinforcement of pro-regenerative fibroblast programs to mitigate scar.
2023-02-23 | PXD035749 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below. Project abstract: In adult mammals, skin wound healing has evolved to favor rapid repair through the formation of fibrotic scar. These dermal scars are dysfunctional and may lead to chronic disfigurement and disability, yet the biologic mechanisms that drive fibrosis and prevent tissue regeneration remain unknown. Here, we report that reindeer (Rangifer tarandus) antler velvet exhibits regenerative wound healing, whereas identical full-thickness injury in dorsal back skin of the same animal forms fibrotic scar. This regenerative capacity is retained even following ectopic transplantation of velvet to a scar-forming site, demonstrating that this latent regenerative capacity is innate to velvet cells and independent of local factors derived from the growing antler. Single cell RNA-sequencing of uninjured skin revealed a marked divergence in resting fibroblast transcriptional states and immunomodulatory function. Uninjured velvet fibroblast shared a striking resemblance with human fetal fibroblasts whereas uninjured back skin fibroblasts exhibited an overrepresentation of pro-inflammatory genes resembling adult human fibroblasts. Identical skin injury resulted in site-specific fibroblast polarization; back fibroblasts exacerbated the inflammatory response, whereas velvet fibroblasts adopted an immunosuppressive state and reverted back to a regeneration-competent ground state. Consequently, velvet wounds exhibited an accelerated adoption of anti-inflammatory immune states and an expedited resolution of immune response. This study demonstrates reindeer as a novel comparative mammalian model to study both adult skin regeneration (velvet) and scar formation (back skin) within the same animal. Our study underscores the importance of fibroblast heterogeneity in shaping local immune cell functions that ultimately polarize wound healing outcomes. Purposeful, acute modulation of fibroblast-mediated immune signaling represents an important therapeutic avenue to mitigate scar and improve wound healing.
2022-12-08 | GSE168748 | GEO
Project description:Therapeutically enabled mammalian kidney repair and regeneration
| PRJNA818306 | ENA
Project description:The kidney has large regenerative capacity that is impeded when injured renal tubular epithelial cells (TECs) undergo SNAI1-driven partial epithelial mesenchymal transition (pEMT). Here we investigate the role of IL11 in TEC pEMT and kidney repair. Wild-type mice with acute kidney injury (AKI) upregulate IL11 in TECs triggering an ERK/P90RSK/GSK3β axis of SNAI1 expression leading to impaired renal function, which is abrogated in Il11 null mice. In mouse models of AKI, a neutralizing IL11 antibody promotes kidney regeneration, while attenuating pEMT, fibrosis and kidney dysfunction. In TECs, TGFβ1 induces autocrine IL11/ERK-dependent pEMT leading to paracrine, IL11-mediated fibroblast activation. Mice with TEC-specific deletion of Il11ra1 are protected from pEMT, inflammation, fibrosis and renal failure. In a mouse model of chronic kidney disease, administration of anti-IL11 reverses fibrosis, regenerates kidney parenchyma and restores renal function. Therapeutic inhibition of IL11 signaling appears permissive for promoting kidney regeneration and improving kidney function.
2022-11-17 | GSE199080 | GEO
Project description:Fibroblasts are the main dermal cell type and are essential for the architecture and function of human skin. Important differences have been described between fibroblasts localized in distinct dermal layers, and these cells are also known to perform varied functions. However, this phenomenon has not been analyzed comprehensively yet. Here we have used single-cell RNA sequencing to analyze >15,000 cells from a sun-protected area in young and old donors. Our results define four main fibroblast subpopulations that can be spatially localized and functionally distinguished. Importantly, intrinsic aging reduces this fibroblast ‘priming’, generates distinct expression patterns of skin aging-associated genes, and substantially reduces the interactions of dermal fibroblasts with other skin cell types. Our work thus provides comprehensive evidence for a functional specialization of human dermal fibroblasts and suggests that the age-related loss of fibroblast priming contributes to human skin aging.
2020-03-31 | GSE130973 | GEO
Project description:Baf155 controls hematopoietic differentiation and regeneration through chromatin priming
| PRJNA1004270 | ENA
Project description:Fibroblast Dedifferentiation as a Determinant of Successful Regeneration
| PRJNA698552 | ENA
Project description:Chromatin priming promotes cell type-specific gene expression, lineage differentiation, and development. The mechanism of chromatin priming has not been well understood. Mouse hematopoietic stem and progenitor cells (HSPCs) lacking the Baf155 subunit of the BAF (BRG1/BRM associated factor) chromatin-remodeler produced a significantly reduced number of mature blood cells, leading to a failure of hematopoietic regeneration upon transplantation and 5-FU injury. Baf155 deficient HSPCs, while showing impaired mature blood cell production, generated a higher frequency of myeloid cells with fewer B and CD8+ T cells at homeostasis, supporting a more immune-suppressive tumor microenvironment and enhanced tumor growth. Single-nuclei multi-omic analysis revealed that Baf155 deficient HSPCs failed to establish accessible chromatin and levels of lineage-specific transcripts were considerably lower. Regions that showed a substantial loss in chromatin accessibility were enriched for enhancers and binding motifs for hematopoietic lineage-specific transcription factors. Our study provides a fundamental mechanistic understanding of the role of Baf155 in establishing chromatin priming with functional consequences in regeneration or tumor immunity.
2024-07-09 | GSE240584 | GEO
Project description:Chromatin priming promotes cell type-specific gene expression, lineage differentiation, and development. The mechanism of chromatin priming has not been well understood. Mouse hematopoietic stem and progenitor cells (HSPCs) lacking the Baf155 subunit of the BAF (BRG1/BRM associated factor) chromatin-remodeler produced a significantly reduced number of mature blood cells, leading to a failure of hematopoietic regeneration upon transplantation and 5-FU injury. Baf155 deficient HSPCs, while showing impaired mature blood cell production, generated a higher frequency of myeloid cells with fewer B and CD8+ T cells at homeostasis, supporting a more immune-suppressive tumor microenvironment and enhanced tumor growth. Single-nuclei multi-omic analysis revealed that Baf155 deficient HSPCs failed to establish accessible chromatin and levels of lineage-specific transcripts were considerably lower. Regions that showed a substantial loss in chromatin accessibility were enriched for enhancers and binding motifs for hematopoietic lineage-specific transcription factors. Our study provides a fundamental mechanistic understanding of the role of Baf155 in establishing chromatin priming with functional consequences in regeneration or tumor immunity.
2024-07-09 | GSE240583 | GEO
Project description:For a short period of time in mammalian neonates, the mammalian heart can regenerate via cardiomyocyte proliferation. This regenerative capacity is largely absent in adults. In other organisms, including zebrafish, damaged hearts can regenerate throughout their lifespans. Many studies have been performed to understand the mechanisms of cardiomyocyte de-differentiation and proliferation during heart regeneration however, the underlying reason why adult zebrafish and young mammalian cardiomyocytes are primed to enter cell cycle have not been identified. Here we show the primed state of a pro-regenerative cardiomyocyte is dictated by its amino acid profile and metabolic state. Adult zebrafish cardiomyocyte regeneration is a result of amino acid-primed mTOR activation. Zebrafish and neonatal mouse cardiomyocytes display elevated glutamine levels, predisposing them to amino acid-driven activation of mTORC1. Injury initiates Wnt/β-catenin signalling that instigates primed mTORC1 activation, Lin28 expression and metabolic remodeling necessary for zebrafish cardiomyocyte regeneration. These studies reveal a unique mTORC1 primed state in zebrafish and mammalian regeneration competent cardiomyocytes.
2022-02-15 | PXD011791 | Pride