ArticleProceedings of the National Academy of Sciences of the United States of America2021
Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Consensus Pituitary Atlas, a scalable resource for annotation, novel marker discovery, and analyses in mouse pituitary gland research.Cell reports · 2026Article
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- The role of stem cells in pituitary tumour formation.Endocrine-related cancer · 2026Review
- A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse.Protein & cell · 2026Article
- Autocrine and paracrine regulation of pituitary endocrine cells.Frontiers in endocrinology · 2026Review
- Spatially selective clearance of inflammation-mediated reactive oxygen species in injured kidney cells.Theranostics · 2026Article
- How stem cells respond to infection, inflammation and ageing.Nature reviews. Immunology · 2025Review
- The Role of Cytokines in the Development and Functioning of the Hypothalamic-Pituitary-Gonadal Axis in Mammals in Normal and Pathological Conditions.International journal of molecular sciences · 2025Review
- New insights in cellular senescence: The pituitary model.Journal of neuroendocrinology · 2025Review
- Single-cell transcriptome atlas of male mouse pituitary across postnatal life highlighting its stem cell landscape.iScience · 2025Article
- High fat diet-induced loss of pituitary plasticity in aging female mice with ablated leptin signaling in somatotropes.Frontiers in endocrinology · 2025Article
- Advancement and Potential Applications of Epididymal Organoids.Biomolecules · 2024Review
- Citrus Flavanone Effects on the Nrf2-Keap1/GSK3/NF-κB/NLRP3 Regulation and Corticotroph-Stress Hormone Loop in the Old Pituitary.International journal of molecular sciences · 2024Article
- Endometrial senescence is mediated by interleukin 17 receptor B signaling.Cell communication and signaling : CCS · 2024Article
- The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases.Experimental hematology & oncology · 2024Review
- Organoids in endocrine and metabolic research: current and emerging applications.Nature reviews. Endocrinology · 2024Article
- Pituitary stem cells: past, present and future perspectives.Nature reviews. Endocrinology · 2024Review
- A narrative review on inflammaging and late-onset hypogonadism.Frontiers in endocrinology · 2024Review
- Single-Cell RNA Sequencing and Its Applications in Pituitary Research.Neuroendocrinology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cells in the adult pituitary are quiescent yet show acute activation upon tissue injury. The molecular mechanisms underlying this reaction are completely unknown. We applied single-cell transcriptomics to start unraveling the acute pituitary stem cell activation process as occurring upon targeted endocrine cell-ablation damage. This stem cell reaction was contrasted with the aging (middle-aged) pituitary, known to have lost damage-repair capacity. Stem cells in the aging pituitary show regressed proliferative activation upon injury and diminished in vitro organoid formation. Single-cell RNA sequencing uncovered interleukin-6 (IL-6) as being up-regulated upon damage, however only in young but not aging pituitary. Administering IL-6 to young mice promptly triggered pituitary stem cell proliferation, while blocking IL-6 or associated signaling pathways inhibited such reaction to damage. By contrast, IL-6 did not generate a pituitary stem cell activation response in aging mice, coinciding with elevated basal IL-6 levels and raised inflammatory state in the aging gland (inflammaging). Intriguingly, in vitro stem cell activation by IL-6 was discerned in organoid culture not only from young but also from aging pituitary, indicating that the aging gland's stem cells retain intrinsic activatability in vivo, likely impeded by the prevailing inflammatory tissue milieu. Importantly, IL-6 supplementation strongly enhanced the growth capability of pituitary stem cell organoids, thereby expanding their potential as an experimental model. Our study identifies IL-6 as a pituitary stem cell activator upon local damage, a competence quenched at aging, concomitant with raised IL-6/inflammatory levels in the older gland. These insights may open the way to interfering with pituitary aging.
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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.