ArticleProceedings of the National Academy of Sciences of the United States of America2010
Lack of p21 expression links cell cycle control and appendage regeneration in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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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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Who cites it
118 citing papers in PubMed, 211 citations in OpenAlex.
- Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans.The Journal of clinical investigation · 2022Trial
- Collection of Wound Exudate From Human Digit Tip Amputations Does Not Impair Regenerative Healing: A Randomized Trial.Medicine · 2015Trial
- p21 Knockdown as a Therapeutic Strategy for Focal Cartilage Injury Repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Identification of Chondrocyte Stemness-Associated Biomarkers in Osteoarthritis Using Bioinformatics and Machine Learning Approaches.Journal of inflammation research · 2026Article
- Carnosic acid in topical rosemary extract enhances skin repair via TRPA1 activation.JCI insight · 2025Article
- Teratoma-free cartilage regeneration using p21-/- iPSCs engineered with iCasp9.Stem cells translational medicine · 2025Article
- The evolution of cancer and ageing: a history of constraint.Nature reviews. Cancer · 2025Review
- Continuous adipose-derived stem cell therapy from the neonatal stage effectively reduces Duchenne muscular dystrophy symptoms in rats.Stem cell research & therapy · 2025Article
- Prx1NPJ Regenerative medicine · 2025Article
- In Vitro Studies of the Effect of Oil Emulsions from Transgenic Flax Varieties on the Treatment of Wound Healing and Care of Human Skin with the Tendency to Inflammation.International journal of molecular sciences · 2025Article
- Age-Associated Activation of the cGAS-STING Pathway and Impairment of DNA Damage Repair in Human Primary Alveolar Type II Cells.Aging and disease · 2025Article
- Disrupted macrophage metabolic adaptation and function drive senescence-induced decline in vertebrate regeneration.Theranostics · 2025Article
- Granulocyte colony stimulating factor promotes scarless tissue regeneration.Cell reports · 2024Article
- Bioinformatics analysis of signature genes related to cell death in keratoconus.Scientific reports · 2024Article
- Absence of E2f1 Negates Pro-osteogenic Impacts of p21 Absence.Calcified tissue international · 2024Article
- Size-Specific Modulation of a Multienzyme Glucosome Assembly during the Cell Cycle.ACS bio & med chem Au · 2023Article
- The superior healing capacity of MRL tendons is minimally influenced by the systemic environment of the MRL mouse.Scientific reports · 2023Article
- Article
- Proximal ear hole injury heals by limited regeneration during the early postnatal phase in mice.Journal of anatomy · 2023Article
- Cell cycle regulators and bone: development and regeneration.Cell & bioscience · 2023Review
58 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Animals capable of regenerating multiple tissue types, organs, and appendages after injury are common yet sporadic and include some sponge, hydra, planarian, and salamander (i.e., newt and axolotl) species, but notably such regenerative capacity is rare in mammals. The adult MRL mouse strain is a rare exception to the rule that mammals do not regenerate appendage tissue. Certain commonalities, such as blastema formation and basement membrane breakdown at the wound site, suggest that MRL mice may share other features with classical regenerators. As reported here, MRL fibroblast-like cells have a distinct cell-cycle (G2/M accumulation) phenotype and a heightened basal and wound site DNA damage/repair response that is also common to classical regenerators and mammalian embryonic stem cells. Additionally, a neutral and alkaline comet assay displayed a persistent level of intrinsic DNA damage in cells derived from the MRL mouse. Similar to mouse ES cells, the p53-target p21 was not expressed in MRL ear fibroblasts. Because the p53/p21 axis plays a central role in the DNA damage response and cell cycle control, we directly tested the hypothesis that p21 down-regulation could functionally induce a regenerative response in an appendage of an otherwise nonregenerating mouse strain. Using the ear hole closure phenotype, a genetically mapped and reliable quantitative indicator of regeneration in the MRL mouse, we show that the unrelated Cdkn1a(tmi/Tyj)/J p21(-/-) mouse (unlike the B6129SF2/J WT control) closes ear holes similar to MRL mice, providing a firm link between cell cycle checkpoint control and 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 OpenQuestion graph.