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An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

ABSTRACT: An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

PROVIDER: PRJNA931237 | ENA |

REPOSITORIES: ENA

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An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained at high levels during complex tissue regeneration. Following ERK inhibition, ear punch regeneration in Acomys shifted towards fibrotic repair. Using scRNA-seq, we identified ERK-responsive cell types. Loss- and gain-of-function experiments prompted us to uncover FGF and ErbB signaling as upstream ERK regulators of regeneration. Strikingly, the ectopic activation of ERK in scar-prone injuries induced a pro-regenerative response, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data detail an important distinction in ERK activity between regenerating and poorly regenerating adult mammals and open avenues to redirect fibrotic repair towards regenerative healing.

2023-04-28 | GSE224879 | GEO

An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained during complex tissue regeneration. Following ERK inhibition, regeneration in Acomys shifted towards a fibrotic repair. Using scRNA-seq, we uncovered that MAPK/ERK signaling acts in a cell type specific manner to direct regenerative healing. Loss- and gain-of-function experiments prompted us to identify FGF and ErbB signaling as upstream ERK regulators of regeneration. By ectopically activating ERK in Mus injuries, a pro- regenerative response was induced, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data provide new insights into why some mammals regenerate better than others and open avenues to redirect fibrotic repair towards regenerative healing.

2023-04-28 | GSE224433 | GEO

An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

Project description:An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

| PRJNA932840 | ENA

An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (<i>Acomys</i>).

Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Now, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate extracellular signal-regulated kinase (ERK) activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained at high levels during complex tissue regeneration. Following ERK inhibition, ear punch regeneration in Acomys shifted toward fibrotic repair. Using single-cell RNA sequencing, we identified ERK-responsive cell types. Loss- and gain-of-function experiments prompted us to uncover fibroblast growth factor and ErbB signaling as upstream ERK regulators of regeneration. The ectopic activation of ERK in scar-prone injuries induced a pro-regenerative response, including cell proliferation, extracellular matrix remodeling, and hair follicle neogenesis. Our data detail an important distinction in ERK activity between regenerating and poorly regenerating adult mammals and open avenues to redirect fibrotic repair toward regenerative healing.

| S-EPMC10132760 | biostudies-literature

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

Spiny mice (Acomys cahirinus) activate unique transcriptional programs after severe kidney injuries and regenerate organ function without fibrosis

Project description:Purpose: The goal of this study was to characterize the kidney transcriptome of Mus musculus and Acomys cahirinus after unilateral ureteral obstruction (UUO) kidney injury. Methods: Kidney mRNA-seq profiles of 10 week old mouse and spiny mouse were generated at 2 day and 5 days after unilateral ureteral obstruction injury in triplicate, using Illumina NovaSeq 6000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Salmon, edgeR and a limma-voom pipeline in R. Results: For both Mus musculus and Acomys cahirinus kidneys, we mapped about 50 million sequence reads per sample to the mouse transcriptome and identified 20580 transcripts in kidneys of Mus musculus and 54075 transcripts in the kidneys of Acomys cahirinus. Using 1.5 fold change and FDR < 0.05, number of transcripts that are significantly different between Mus musculus samples: 3915 between normal and day 2 after UUO, 5365 between normal and day 5 after UUO. For Acomys cahirinus: 1765 between normal and day 2 after UUO, 2499 between normal and day 5 after UUO. Conclusions: Our study demonstrate there were many conserved responses to kidney injury between M. musculus and A. cahirinus despite the divergent outcomes for kidney fibrosis.

2021-09-13 | GSE168876 | GEO

Acomys

Project description:Acomys Raw sequence reads

| PRJNA323834 | ENA

Acomys cahirinus

Project description:Acomys cahirinus overview

| PRJNA188251 | ENA

Acomys cahirinus

Project description:Spiny mouse (Acomys cahirinus) embryo RNA-Seq (2-cell, 4-cell and 8-cell stages n=4 of each)

| PRJNA436818 | ENA

Comparing regeneration and fibrosis using Acomys and Mus

Project description:This project is designed to find differentially expressed genes between regeneration and fibrosis in Acomys (regenerator) and Mus (non-regenerator)

2016-03-17 | GSE71761 | GEO

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