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Comparative Transcriptomic Analysis of Dermal Wound Healing Reveals De Novo Skeletal Muscle Regeneration in Acomys cahirinus

ABSTRACT: This project is a comprehensive analysis of gene expression following full-thickness excisional dermal wounds in the African spiny mouse and the laboratory mouse.

ORGANISM(S): Mus musculus Acomys cahirinus

PROVIDER: GSE113081 | GEO | 2019/04/25

REPOSITORIES: GEO

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Comparative transcriptomic analysis of dermal wound healing reveals de novo skeletal muscle regeneration in Acomys cahirinus.

Project description:The African spiny mouse, Acomys spp., is capable of scar-free dermal wound healing. Here, we have performed a comprehensive analysis of gene expression throughout wound healing following full-thickness excisional dermal wounds in both Acomys cahirinus and Mus musculus. Additionally, we provide an annotated, de novo transcriptome assembly of A. cahirinus skin and skin wounds. Using a novel computational comparative RNA-Seq approach along with pathway and co-expression analyses, we identify enrichment of regeneration associated genes as well as upregulation of genes directly related to muscle development or function. Our RT-qPCR data reveals induction of the myogenic regulatory factors, as well as upregulation of embryonic myosin, starting between days 14 and 18 post-wounding in A. cahirinus. In contrast, the myogenic regulatory factors remain downregulated, embryonic myosin is only modestly upregulated, and no new muscle fibers of the panniculus carnosus are generated in M. musculus wounds. Additionally, we show that Col6a1, a key component of the satellite cell niche, is upregulated in A. cahirinus compared to M. musculus. Our data also demonstrate that the macrophage profile and inflammatory response is different between species, with A. cahirinus expressing significantly higher levels of Il10. We also demonstrate differential expression of the upstream regulators Wnt7a, Wnt2 and Wnt6 during wound healing. Our analyses demonstrate that A. cahirinus is capable of de novo skeletal muscle regeneration of the panniculus carnosus following removal of the extracellular matrix. We believe this study represents the first detailed analysis of de novo skeletal muscle regeneration observed in an adult mammal.

| S-EPMC6541261 | biostudies-literature

Comparing the transcriptome of early and late phase wound macrophages in skin

Project description:We inflicted full thickness excisional wounds in the back skin of C57BL/6 wild-type mice. Injury-associated macrophages were isolated from wound tissue during the early inflammatory phase (4 days post injury) and in the late, scar forming phase (14 days post injury), sorted by flow cytometry (CD45+CD11b+F4/80+ wound cells), and subjected to RNAsequencing.

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Changes in transcriptome during excisional cutaneous murine wound healing

Project description:Using microarray analysis, we explored the differences in gene expression in wounded and intact skin using murine model. Injured skin samples were examined at days 1 and 4 post injury. The results provide the detailed molecular profile of the the genetic response to injury. Two full-thickness dermal wounds were made on the opposite sides of the midline of each mouse using a 4 mm punch biopsy instrument. Wounds were made through the epidermis, dermis, and subcutaneous tissue layers while leaving the fascia intact. At a specified time point after the wounding (1 and 4 days), mice were sacrificed by carbon dioxide inhalation. The wounds and surrounding tissues or intact skin samples were removed with an 8 mm biopsy punch.

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Newly defined ABCB5+ dermal mesenchymal stem cells promote healing of chronic iron overload wounds via secretion of interleukin-1 receptor antagonist

Project description:Here we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of non-healing wounds. Local administration of dermal ABCB5+-derived MSCs attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron overload mouse model mimicking the non-healing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+-derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained pro-inflammatory M1 macrophages towards repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+-derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγnull mice. In conclusion, human dermal ABCB5+ cells represent a novel, easy accessible and marker-enriched source of MSCs which holds substantial promise to successfully treat chronic non-healing wounds in humans.

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Human Skin Transcriptome during Epidermal Wound Healing

Project description:In order to clarify the human response of re-epithelialization, we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. Altogether 25 biopsies from 8 patients qualified for the study. All samples were analysed by genome-wide microarrays. Here we identified the genes associated with normal skin re-epithelialization on time-scale, and organized them by similarities according to their induction or suppression patterns during wound healing. Overall 25 samples were analyzed

2011-04-29 | E-GEOD-28914 | biostudies-arrayexpress

Transcription profiling by array of excisional biopsy wounds from young and old human subjects to measure the influence of age on cutaneous wound healing

Project description:The aim of this experiment was measure the influence of age on cutaneous wound healing using human subjects. Increaded age has been associated with delayed wound healing in mouse models and in humans. Gene expression was compared between excisional biopsy wounds from young and old subjects.

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Human Skin Transcriptome during Epidermal Wound Healing

2011-04-29 | GSE28914 | GEO

microRNA expression in skin and wound edge tissue at different time points

Project description:Change in miRNA expression pattern during different phases of wound healing following full thickness excisional wounding was studied.

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A Comparative Analysis of Gene Expression Profiles During Skin Regeneration in Mus and Acomys

Project description:Acomys exhibits a blunted immune response to wounding, and shares characteristics with fetal wound healing We used mouse microarrays to compare gene expression profiles during wound healing between the African spiny mouse (Acomys) and the house mouse (Mus)

2015-10-28 | E-GEOD-74387 | biostudies-arrayexpress

Project description:Ageing-related delays in wound healing are well-documented in both human and animal models. However, the mechanisms underlying this impairment in healing progression are not fully understood. In this study, we characterised ageing-associated changes to the structure and function of the skin in young and aged mice and investigated the cellular differences that impacted the progression of wound healing. Full-thickness wounds created on the dorsum of C57BL/6J young and aged mice were excised on Day 0, Day 3 and Day 7 post-wounding for analysis by immunohistochemistry, flow cytometry, RNA sequencing. Our data revealed that macrophages were significantly reduced in aged wounds in comparison to young. Functional transcriptomic analyses showed that macrophages from aged wounds exhibited significantly reduced expression of cell cycle, DNA replication, and repair pathway genes. Furthermore, we uncovered an elevated pro-inflammatory gene expression program in the aged macrophages linked to poor inflammation resolution and excessive tissue damage observed in aged wounds. Altogether, our work provides insights into how poorly healing aged wounds are phenotypically defined by the presence of macrophages with reduced proliferative capacity and an exacerbated inflammatory response, both of which are pathways that can be targeted to improve healing in the elderly.

2022-06-24 | GSE199763 | GEO

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