Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hyperinnervation inhibits organ-level regeneration in mammalian skin

ABSTRACT: Some mammalian tissues can replace lost cells within one lineage, but organ-level regeneration—restoring diverse cell types across lineages—remains rare. Here we show that late embryonic full-thickness skin injuries heal by regenerating epithelial, mesenchymal, neuronal, and vascular lineages with proper connectivity. However, this ability is lost soon after birth, leading to a failure to restore most cell types and hyperinnervation of the wound bed. Single-cell sequencing identified a postnatal wound-specific fibroblast (PWF) population absent after embryonic wounding. Through an in vivo screen, we discovered three PWF-enriched genes—Timp1, Cxcl12, and Ccl7—that inhibit organ-level regeneration and cause hyperinnervation when overexpressed in embryonic wounds. Reducing hyperinnervation by depleting Cxcl12 in fibroblasts or inhibiting synaptic release enables postnatal skin to regenerate diverse lineages after injury. Our study identifies mechanisms transitioning an organ from regenerative to non-regenerative, discovers fibroblast-driven hyperinnervation as a key barrier, and demonstrates removing this barrier unlocks organ-level regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE276119 | GEO | 2026/03/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hyperinnervation inhibits organ-level regeneration in mammalian skin

Project description:Hyperinnervation inhibits organ-level regeneration in mammalian skin

| PRJNA1154938 | ENA

Gene expression in feather dermal papilla (DP)

Project description:The feather follicle is a “professional” regenerative organ that undergoes natural cycling and, regeneration after wound plucking. Similar to mammalian hair follicle, dermal papilla (DP) controls feather regeneration, shape, size, and axis. Here we report gene expression profiling for feather DP at different growth stages. For growth phase, we compared gene expression of DP, the ramogenic zone of feather branching epithelium (Erz) and the mesenchymal pulp (Pp). We also compared gene expression of DP at resting phase. To characterize the feather regeneration process, we further profiled gene expression at Day-2 and Day-4 post wound. Our results provide a resource for investigating feather growth and regeneration. Examination of gene expression in dermal papilla (DP) at growth phase and resting phase feather follicle, and during feather regeneration.

2014-01-22 | E-GEOD-42017 | biostudies-arrayexpress

Glucocorticoid treatment leads to aberrant ion and macromolecular transport mechanisms in regenerating zebrafish fins.

Project description:Bone is a highly regenerative tissue but it can be permanently lost due to severe trauma and as a result of disease. In zebrafish, which are capable of complex organ regeneration, intramembranous bones of the fins and skull regenerate rapidly even after profound loss. The fin regenerate, albeit being composed of different tissues is a structure of modest complexity which, together with the fact that it is easy to access and monitor, makes it a useful system to study bone formation, wound healing and metabolic disease. Glucocorticoids are powerful drugs used in anti-inflammatory and immunosuppressive therapy. Despite their unmistakable advantages and usefulness, long term treatment with glucocorticoids can cause a variety of adverse effects such as insulin resistance, high blood pressure and bone fragility. Here we made use of proteomics to study the fin regeneration by sampling zebrafish caudal fins without prior injury and regenerated tissue 4 days post amputation at normal and perturbed conditions (prednisolone-treatment).

2019-09-26 | PXD013552 | Pride

Gene expression in feather dermal papilla (DP)

2014-01-22 | GSE42017 | GEO

Human fingertip regeneration follows clinical phases with distinct proteomic signatures

Project description:Distal injuries in human fingertips can regenerate almost fully, yet the process of human fingertip regeneration has hardly been characterized on a cellular and molecular level. A silicone finger cap, comprising a puncturable reservoir, was used to treat 22 human fingertip amputations. In all patients, subcutaneous tissue, nailbed and skin regenerated with excellent outcomes. Through the clinical assessment of the wounds, the regenerative process was divided into four distinct phases. Proteomic data from wound fluid samples collected at regular intervals, confirmed robust and unbiasedly distinct proteomic signatures, characteristic processes, and active regulatory networks in each phase. Moreover, this human dataset provides important insights, showing clear divergences from findings in regenerative animal models. The longitudinal and comprehensive analysis presented here unveils the complex orchestration of four clinically and proteomically-distinct phases of human fingertip regeneration. Further analyses of this proteomic data will allow for the identification of candidates orchestrating human fingertip regeneration and serving as a framework for comparative and regenerative medicine studies.

2025-11-05 | PXD067200 | Pride

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [scRNA-seq]

Project description:Niche-associated signals, essential for the maintenance of normal stem cells and tumor-initiating cells, are spatially confined and exert their influence locally among adjacent cells. Here, we demonstrate that CXCR4+ macrophages are enriched in the normal mammary ducts and enhance regenerative activity in basal cells in response to the CXCL12 secreted by luminal cells. Conditional knockout of CXCR4 in macrophages or CXCL12 in luminal cells results in similar phenotypes, including impaired branching morphogenesis, decreased regenerative functionality in basal cells, and diminished ductal association of macrophages. CXCL12 stimulation of macrophages triggers an AKT-mediated stabilization of β-catenin, increasing the expression of pro-migratory genes and multiple Wnt ligands, which enhances the infiltration of macrophages and their ability to support stem-like regenerative functions of basal cells. Importantly, the identical CXCR4+ niche macrophages also govern the tumor-initiating activity of breast tumors by promoting the survival and tumor-forming capacity of tumor-initiating cells and inducing early immune evasion through the accumulation of regulatory T cells. Our findings elucidate a crucial role of the CXCL12-CXCR4 axis in facilitating a complex interaction among niche macrophages, two mammary epithelial cell lineages, and other stromal components, thereby establishing a supportive environment for both normal tissue regeneration and mammary tumor initiation.

2025-04-15 | GSE275907 | GEO

CXCL12-CXCR4 signaling mediates the formation of a macrophageal niche for mammary tumorigenesis [tumor]

2025-04-15 | GSE275906 | GEO

Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing

Project description:Regeneration is the “holy grail” of tissue repair, but skin injury typically yields fibrotic, non-functional scars. Developing pro-regenerative therapies requires rigorous understanding of the molecular progression from injury to fibrosis or regeneration. Here, we report the divergent molecular events driving skin wound cells toward either scarring or regenerative fates. We profile scarring versus YAP inhibition-induced wound regeneration at the transcriptional (single-cell RNA-sequencing), protein (timsTOF proteomics), and tissue (extracellular matrix ultrastructural analysis) levels. Using cell surface barcoding, we integrate these data to reveal fibrotic and regenerative “molecular trajectories” of healing. We show that disrupting YAP mechanical signaling yields regenerative repair orchestrated by fibroblasts with activated Trps1 and Wnt signaling. Finally, by performing in vivo gene knockdown and overexpression in wounds, we identify Trps1 as a key regulatory gene that is necessary and partially sufficient for wound regeneration. Our findings serve as a multimodal map of wound regeneration and could have therapeutic implications for pathologic fibroses.

2022-01-24 | GSE186527 | GEO

Restoring Bone Regeneration in Critical Size Defects through Local Delivery of Angiogenic Factors

Project description:Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients’ quality of life and mental well-being.To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealednotable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we applied locally delivered Spp1 and Cxcl12 embedded PCL scaffolds in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.

2024-08-08 | GSE262544 | GEO

JAK/STAT coordinates cell proliferation during disc regeneration with Dilp8-mediated developmental delay in Drosophila melanogaster

Project description:Regeneration of fragmented Drosophila imaginal discs occurs in an epimorphic manner, involving local cell proliferation at the wound site. Following disc fragmentation, cells at the wound site activate a restoration program through wound healing, regenerative cell proliferation and repatterning of the tissue. However, the interplay of signaling cascades, driving these early reprogramming steps, is not well understood. Here we profiled the transcriptome of regenerating cells in the early phase within twenty-four hours after wounding. We found that JAK/STAT signaling becomes activated at the wound site and promotes regenerative cell proliferation in cooperation with Wingless (Wg) signaling. In addition, we demonstrated that the expression of Drosophila insulin-like peptide 8 (dilp8), which encodes a paracrine peptide to delay the onset of pupariation, is controlled by JAK/STAT signaling in early regenerating discs. Our findings suggest that JAK/STAT signaling plays a pivotal role in coordinating regenerative disc growth with organismal developmental timing. In order to analyze transcriptome change in early regenerating imaginal disc, Drosophila prothorasic leg discs were fragmented (to anterior one-quarter or posterior three-quarters) and cultured ex vivo in adult fly abdomen. Regenerating cells in early regeneration phase (at 12 or 24 hours after wounding) were subjected to transcriptome profiling with Affymetrix microarrays. For control samples, the corresponding regions of uncut-cultured discs and uncut-uncultured discs were used.

2015-04-10 | E-GEOD-54868 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data