ArticlePLoS biology2010
Quiescent fibroblasts exhibit high metabolic activity.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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Who cites it
238 citing papers in PubMed, 386 citations in OpenAlex.
- Circulating lipids, lipoproteins, and the risk of idiopathic pulmonary fibrosis: a cohort study and genetic analysis.Journal of lipid research · 2026Article
- Sparse Cell Labeling Reveals Morphologic Diversity Among Mouse Scleral Fibroblasts.Investigative ophthalmology & visual science · 2026Article
- Crystalline and Amorphous Cerium Phosphate Nanoparticles as Enzyme-Mimetic Nanomaterials for Regenerative Medicine.Nanomaterials (Basel, Switzerland) · 2026Article
- [European journal of nuclear medicine and molecular imaging · 2026Article
- The effect of macromolecular crowders as a supplement to serum free media on human corneal stromal cells proliferation and marker expression.Scientific reports · 2026Article
- Single-cell insights into hepatic fibroblasts and stellate cells: heterogeneity in matrix remodelling in development, health, and disease.Npj gut and liver · 2026Review
- An Alternative Metabolic Pathway of Glucose Oxidation Induced by Mitochondrial Complex I Inhibition: Serinogenesis and Folate Cycling.International journal of molecular sciences · 2025Article
- Active mitochondria in healthy spiny mouse fibroblasts resemble megamitochondria and remain resilient across lifespan.bioRxiv : the preprint server for biology · 2025Article
- miRNAs in Pulmonary Hypertension: Mechanistic Insights and Therapeutic Potential.Biomedicines · 2025Review
- Starvation activates ECM-remodeling gene transcription and putative enhancers in fibroblasts despite inducing quiescence.Cell reports · 2025Article
- Impact of Poly(Lactic Acid) and Graphene Oxide Nanocomposite on Cellular Viability and Proliferation.Pharmaceutics · 2025Article
- Generation of mature epicardium derived from human-induced pluripotent stem cells via inhibition of mTOR signaling.Nature communications · 2025Article
- Article
- Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups.Scientific reports · 2025Article
- Altered Fibroblast Glutamine Metabolism Is Linked to the Severity of Cardiac Dysfunction in DCMA, a Mitochondrial Cardiomyopathy.Journal of inherited metabolic disease · 2025Article
- Same same but different? How blood and lymphatic vessels induce cell contact inhibition.Biochemical Society transactions · 2025Review
- Transcription factor networks in cellular quiescence.Nature cell biology · 2025Review
- The lactylation-macrophage interplay: implications for gastrointestinal disease therapeutics.Frontiers in immunology · 2025Review
- Spherical Manifolds Capture Drug-Induced Changes in Tumor Cell Cycle Behavior.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- Distribution and morphologic characterization of telocytes in rat ovary and uterus: insights from ultrastructural and immunohistochemical analysis.Histochemistry and cell biology · 2024Article
178 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Many cells in mammals exist in the state of quiescence, which is characterized by reversible exit from the cell cycle. Quiescent cells are widely reported to exhibit reduced size, nucleotide synthesis, and metabolic activity. Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes. In contrast, we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition. By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data, we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells, with greater overflow flux from the pentose phosphate pathway back to glycolysis. Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts. By feeding the cells labeled glutamine, we also detected a "backwards" flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis. The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid, and in part toward excretion of extracellular matrix proteins. Thus, reduced metabolic activity is not a hallmark of the quiescent state. Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole.
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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.