ArticleThe Journal of clinical investigation2017
Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 32 citations in OpenAlex.
- EMP1 safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and alleviating endoplasmic reticulum stress.Nature communications · 2025Article
- The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitness.Nature communications · 2024Article
- 27-Hydroxycholesterol Negatively Affects the Function of Bone Marrow Endothelial Cells in the Bone Marrow.International journal of molecular sciences · 2024Article
- Rag-GTPase-TFEB/TFE3 axis controls B cell mitochondrial fitness and humoral immunity independent of mTORC1.Research square · 2024Article
- The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitness.bioRxiv : the preprint server for biology · 2024Article
- A conserved nutrient responsive axis mediates autophagic degradation of miRNA-mRNA hybrids in blood cell progenitors.Nucleic acids research · 2024Article
- Metabolism in Hematopoiesis and Its Malignancy.Advances in experimental medicine and biology · 2023Article
- Role of reactive oxygen species in regulating 27-hydroxycholesterol-induced apoptosis of hematopoietic progenitor cells and myeloid cell lines.Cell death & disease · 2022Article
- SZT2 maintains hematopoietic stem cell homeostasis via nutrient-mediated mTORC1 regulation.The Journal of clinical investigation · 2022Article
- You are what you eat: How to best fuel your immune system.Frontiers in immunology · 2022Review
- Inhibition of Rag GTPase signaling in mice suppresses B cell responses and lymphomagenesis with minimal detrimental trade-offs.Cell reports · 2021Article
- Mitochondria Turnover and Lysosomal Function in Hematopoietic Stem Cell Metabolism.International journal of molecular sciences · 2021Review
- Amino acids and RagD potentiate mTORC1 activation in CD8Journal for immunotherapy of cancer · 2021Article
- Metabolite sensing and signaling in cancer.The Journal of biological chemistry · 2020Review
- Dynamic responses of the haematopoietic stem cell niche to diverse stresses.Nature cell biology · 2020Review
- Amino Acids License Kinase mTORC1 Activity and Treg Cell Function via Small G Proteins Rag and Rheb.Immunity · 2019Article
- Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells.International journal of molecular sciences · 2019Article
- Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity.Experimental hematology · 2018Article
- The hematopoietic stem cell diet.International journal of hematology · 2018Review
- Mammalian sterile 20 kinase 1 and 2 are important regulators of hematopoietic stem cells in stress condition.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity. Here, we have evaluated differential nutrient-sensing dependence through RagA and mTORC1 in hematopoietic progenitors, which dynamically drive mature cell production, and hematopoietic stem cells (HSC), which provide a quiescent cellular reserve. In nutrient-abundant conditions, RagA-deficient HSC were functionally unimpaired and upregulated mTORC1 via nutrient-insensitive mechanisms. RagA was also dispensable for HSC function under nutritional stress conditions. Similarly, hyperactivation of RagA did not affect HSC function. In contrast, RagA deficiency markedly altered progenitor population function and mature cell output. Therefore, RagA is a molecular mechanism that distinguishes the functional attributes of reactive progenitors from a reserve stem cell pool. The indifference of HSC to nutrient sensing through RagA contributes to their molecular resilience to nutritional stress, a characteristic that is relevant to organismal viability in evolution and in modern HSC transplantation approaches.
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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.