ArticleeLife2022
Spatial transcriptomics reveals metabolic changes underly age-dependent declines in digit regeneration.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- SpatialFlux: an R package for distance gradient analysis in spatial transcriptomics.Bioinformatics (Oxford, England) · 2026Article
- Macrophage metabolism directs regenerative versus fibrotic healing through BMP signaling in the mouse digit tip.bioRxiv : the preprint server for biology · 2026Article
- Review
- Targeting lymphatic vessels enhances bone regeneration by augmenting osteoclast activity in mouse models of amputation.The Journal of clinical investigation · 2026Article
- Advances in Spatial Transcriptomics in Bone.Current osteoporosis reports · 2026Review
- Osteoimmune senescence in aging-related bone diseases.Frontiers in immunology · 2026Review
- Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics.Communications biology · 2025Article
- Skeletal Maturity and Age-Related Changes in Immune Cells and Circulatory Factors Impair Large-Scale Bone Regeneration.Aging cell · 2025Article
- Ageing versus developmental silencing: Answers from the epigenome.The FEBS journal · 2025Review
- Multi-omics approach reveals TGF-β signaling-driven senescence in periodontium stem cells.Journal of advanced research · 2025Article
- Current Role and Future Frontiers of Spatial Transcriptomics in Genitourinary Cancers.Cancers · 2025Review
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Advancing muscle aging and sarcopenia research through spatial transcriptomics.Osteoporosis and sarcopenia · 2025Review
- Advances in spatial transcriptomics and its application in the musculoskeletal system.Bone research · 2025Review
- Osteoprogenitor cells from non-regenerative bone show greater resistance to cellular stress than those from regenerative bone.Frontiers in cell and developmental biology · 2025Article
- STimage-1K4M: A histopathology image-gene expression dataset for spatial transcriptomics.Advances in neural information processing systems · 2024Article
- Characterization of regeneration initiating cells during Xenopus laevis tail regeneration.Genome biology · 2024Article
- Developmental stage dependent effects of posterior and germline regeneration on sexual maturation in Platynereis dumerilii.Developmental biology · 2024Article
- Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.JCI insight · 2024Article
- Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.Military Medical Research · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
De novo limb regeneration after amputation is restricted in mammals to the distal digit tip. Central to this regenerative process is the blastema, a heterogeneous population of lineage-restricted, dedifferentiated cells that ultimately orchestrates regeneration of the amputated bone and surrounding soft tissue. To investigate skeletal regeneration, we made use of spatial transcriptomics to characterize the transcriptional profile specifically within the blastema. Using this technique, we generated a gene signature with high specificity for the blastema in both our spatial data, as well as other previously published single-cell RNA-sequencing transcriptomic studies. To elucidate potential mechanisms distinguishing regenerative from non-regenerative healing, we applied spatial transcriptomics to an aging model. Consistent with other forms of repair, our digit amputation mouse model showed a significant impairment in regeneration in aged mice. Contrasting young and aged mice, spatial analysis revealed a metabolic shift in aged blastema associated with an increased bioenergetic requirement. This enhanced metabolic turnover was associated with increased hypoxia and angiogenic signaling, leading to excessive vascularization and altered regenerated bone architecture in aged mice. Administration of the metabolite oxaloacetate decreased the oxygen consumption rate of the aged blastema and increased WNT signaling, leading to enhanced in vivo bone regeneration. Thus, targeting cell metabolism may be a promising strategy to mitigate aging-induced declines in tissue regeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.