ArticleScientific reports2019
mTORC1 and mTORC2 Differentially Regulate Cell Fate Programs to Coordinate Osteoblastic Differentiation in Mesenchymal Stromal Cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
23 citing papers in PubMed, 84 citations in OpenAlex.
- High cut-off dialysis mitigates pro-calcific effects of plasma on vascular progenitor cells.Scientific reports · 2021Trial
- Everolimus suppresses glucose transporter 3 membrane trafficking to improve therapeutic efficacy of umbilical cord blood-derived mesenchymal stem cell transplantation in diabetic retinopathy.Cell death & disease · 2026Article
- The steroid hormone 20-hydroxyecdysone inhibits RAPTOR expression by repressing Hox gene transcription to induce autophagy.The Journal of biological chemistry · 2025Article
- Exploration of potential biomarkers and immune cell infiltration characteristics for peripheral atherosclerosis in sjögren's syndrome based on comprehensive bioinformatics analysis and machine learning.Frontiers in genetics · 2025Article
- A Mesenchymal stem cell Aging Framework, from Mechanisms to Strategies.Stem cell reviews and reports · 2024Review
- Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy.Cell communication and signaling : CCS · 2024Article
- Activating Wnt/β-catenin signaling by autophagic degradation of APC contributes to the osteoblast differentiation effect of soy isoflavone on osteoporotic mesenchymal stem cells.Acta pharmacologica Sinica · 2023Article
- Hyperbaric oxygen treatment increases intestinal stem cell proliferation through the mTORC1/S6K1 signaling pathway in Mus musculus.Biological research · 2023Article
- Targeted degradation of ⍺-synuclein aggregates in Parkinson's disease using the AUTOTAC technology.Molecular neurodegeneration · 2023Article
- Rapamycin-filgrastim combination therapy ameliorates portal hypertension-induced splenomegaly: Role of β actin and S100A9 proteins modulation.Iranian journal of basic medical sciences · 2022Article
- The Active Compound Thymoquinone Alters Chondrogenic Differentiation of Human Mesenchymal Stem Cells via Modulation of Intracellular Signaling.Medeniyet medical journal · 2022Article
- The use of non-model Drosophila species to study natural variation in TOR pathway signaling.PloS one · 2022Article
- The mTOR inhibitor Rapamycin protects from premature cellular senescence early after experimental kidney transplantation.PloS one · 2022Article
- Role of the major histocompatibility complex class II protein presentation pathway in bone immunity imbalance in postmenopausal osteoporosis.Frontiers in endocrinology · 2022Review
- Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells.Frontiers in genetics · 2022Review
- Multiple functions of autophagy in vascular calcification.Cell & bioscience · 2021Review
- mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership.International journal of molecular sciences · 2021Review
- mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target.International journal of molecular sciences · 2021Review
- T-Cell Mediated Inflammation in Postmenopausal Osteoporosis.Frontiers in immunology · 2021Review
- Single-Cell Atlas Reveals Fatty Acid Metabolites Regulate the Functional Heterogeneity of Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Vascular regeneration depends on intact function of progenitors of vascular smooth muscle cells such as pericytes and their circulating counterparts, mesenchymal stromal cells (MSC). Deregulated MSC differentiation and maladaptive cell fate programs associated with age and metabolic diseases may exacerbate arteriosclerosis due to excessive transformation to osteoblast-like calcifying cells. Targeting mTOR, a central controller of differentiation and cell fates, could offer novel therapeutic perspectives. In a cell culture model for osteoblastic differentiation of pluripotent human MSC we found distinct roles for mTORC1 and mTORC2 in the regulation of differentiation towards calcifying osteoblasts via cell fate programs in a temporally-controlled sequence. Activation of mTORC1 with induction of cellular senescence and apoptosis were hallmarks of transition to a calcifying phenotype. Inhibition of mTORC1 with Rapamycin elicited reciprocal activation of mTORC2, enhanced autophagy and recruited anti-apoptotic signals, conferring protection from calcification. Pharmacologic and genetic negative interference with mTORC2 function or autophagy both abolished regenerative programs but induced cellular senescence, apoptosis, and calcification. Overexpression of the mTORC2 constituent rictor revealed that enhanced mTORC2 signaling without altered mTORC1 function was sufficient to inhibit calcification. Studies in mice reproduced the in vitro effects of mTOR modulation with Rapamycin on cell fates in vascular cells in vivo. Amplification of mTORC2 signaling promotes protective cell fates including autophagy to counteract osteoblast differentiation and calcification of MSC, representing a novel mTORC2 function. Regenerative approaches aimed at modulating mTOR network activation patterns hold promise for delaying age-related vascular diseases and treatment of accelerated arteriosclerosis in chronic metabolic conditions.
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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.