Whole-transcriptome analysis illustrates evolving transcriptional human response to injury in acute wounds and scars
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE178411 | GEO | 2024/06/03
REPOSITORIES: GEO
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Project description:Full thickness and deep partial thickness burn injuries heal by scarring. There are several mechanisms thought to be essential for the development of burn scars, but a challenge to studying the skin response to burn injury is that there are few animal models of burn scarring that are either clinically similar to human burn scars or are practical for most investigators to use. The purpose of this study was to examine the changes in RNA expression in human skin to burn injury. This was done by comparing pre-injury tissue from otherwise healthy adults undergoing aesthetic scarification created by branding with a hot metal object to serial samples of untreated wounds in the same subjects.
2014-01-22 | E-MTAB-1323 | biostudies-arrayexpress
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:Marjolin's ulcer is a a rare and aggressive cutaneous malignancy that can arise on previously injured skin, established scars, and chronic non-healing wounds. It is most often found in burn scars, but it can also occur in other types of wounds, including venous stasis ulcers, pressure sores, and vaccination sites. The most common histological type of Marjolin’s ulcers is squamous cell carcinoma, however basal cell carcinomas, malignant melanomas, and sarcomas have also been reported. All parts of the body could potentially be affected yet the lower extremities are the anatomic sites most commonly involved. While SCCs commonly have a metastasis rate of 0.5 to 3.0 percent, those arising from burn scars metastasize at a rate in excess of 30 percent. The 5-year survival after a diagnosis of Marjolin’s ulcer was found to be 50 percent. The transformation to a malignancy can occur either chronically, over a period of more than 35 years, or occasionally within a year of the original injury. The exact mechanism of this transformation is not fully understood, but it is thought to be related to chronic keratinocyte dysfunction during the healing process of severe burn wounds. Surgical excision is the main treatment for Marjolin's ulcer and provides the best chance of survival. In a previous study, we investigated the bulk transcriptional changes that lead to Marjolin's ulcer by comparing global gene expression changes between squamous cells present in a squamous cell carcinoma versus those present within Marjolin's ulcer (MU) (Sinha et. al. JBCR 2017). This imparted novel insights into mechanisms underlying divergent clinical features of these cutaneous cancers. The goal of our current study is to characterize a new case of Marjolin's ulcer in a patient under our care by analyzing the cell types, their frequencies, and their individual transcriptional responses within a burn scar versus within Marjolin's ulcer. To achieve this, we conducted single-cell RNA sequencing on two excised tissues: 1. a sample from the center of the tumor (tumor core), and 2. another sample from the margin of tumor-free scar tissue.
2024-07-21 | GSE251937 | GEO
Project description:Marjolin's ulcer is a a rare and aggressive cutaneous malignancy that can arise on previously injured skin, established scars, and chronic non-healing wounds. It is most often found in burn scars, but it can also occur in other types of wounds, including venous stasis ulcers, pressure sores, and vaccination sites. The most common histological type of Marjolin’s ulcers is squamous cell carcinoma, however basal cell carcinomas, malignant melanomas, and sarcomas have also been reported. All parts of the body could potentially be affected yet the lower extremities are the anatomic sites most commonly involved. While SCCs commonly have a metastasis rate of 0.5 to 3.0 percent, those arising from burn scars metastasize at a rate in excess of 30 percent. The 5-year survival after a diagnosis of Marjolin’s ulcer was found to be 50 percent. The transformation to a malignancy can occur either chronically, over a period of more than 35 years, or occasionally within a year of the original injury. The exact mechanism of this transformation is not fully understood, but it is thought to be related to chronic keratinocyte dysfunction during the healing process of severe burn wounds. Surgical excision is the main treatment for Marjolin's ulcer and provides the best chance of survival. In a previous study, we investigated the bulk transcriptional changes that lead to Marjolin's ulcer by comparing global gene expression changes between squamous cells present in a squamous cell carcinoma versus those present within Marjolin's ulcer (MU) (Sinha et. al. JBCR 2017). This imparted novel insights into mechanisms underlying divergent clinical features of these cutaneous cancers. The goal of our current study is to characterize a new case of Marjolin's ulcer in a patient under our care by analyzing the cell types, their frequencies, and their individual transcriptional responses within a burn scar versus within Marjolin's ulcer. To achieve this, we conducted single-cell RNA sequencing on two excised tissues: 1. a sample from the center of the tumor (tumor core), and 2. another sample from the margin of tumor-free scar tissue.
2024-07-21 | GSE234919 | GEO
Project description:Keloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes. Skin and scar tissues were obtained for isolation of primary keratinocytes and fibroblasts. Keloid scars were excised from patients undergoing scar excision surgery, normal skin samples were isolated from patients undergoing elective plastic surgery. Primary culters were prepared for keratinocytes and fibroblasts, and were harvested for analysis up to passage three. Nine keloid scars, for adjacent non-lesional keloid skin samples, and three normal skin samples were obtained and cultured. RNA was isolated using RNeasy, and quality verified using an Agilent 2100 Bioanalyzer. Labeling and hybridization to Affymetrix Human Gene 1.0 ST microarray chips was performed by the Vanderbilt Genome Sciences Resource at Vanderbilt University Medical Center.
2013-05-28 | E-GEOD-44270 | biostudies-arrayexpress
Project description:Hypertrophic scars (HTS) are fibrotic skin disorders characterized by excessive deposition of dermal extracellular matrix (ECM), presenting significant challenges in clinical management despite incomplete understanding of their underlying mechanisms. Using MeRIP-seq and RNA-seq, our study initially revealed the direct regulatory role of ALKBH5 on ECM components in dermal fibroblasts, thereby involving in the pathogenesis of HTS.
2024-09-13 | GSE264743 | GEO
Project description:Hypertrophic scars (HTS) are fibrotic skin disorders characterized by excessive deposition of dermal extracellular matrix (ECM), presenting significant challenges in clinical management despite incomplete understanding of their underlying mechanisms. Using MeRIP-seq and RNA-seq, our study initially revealed the direct regulatory role of ALKBH5 on ECM components in dermal fibroblasts, thereby involving in the pathogenesis of HTS.
2024-09-13 | GSE264515 | GEO
Project description: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 | GSE207021 | GEO
Project description: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 | GSE142854 | GEO
Project description: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 | GSE176360 | GEO