{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T22:06:51Z","timestamp":1772921211954,"version":"3.50.1"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, and changes in nutrient pools and fluxes are important components of the bidirectional communication between MSCs and hematological cancer cells. Among nutrients, amino acids play a significant role in cancer progression and chemo-resistance. Moreover, selected types of cancer cells are extremely greedy for glutamine, and significantly deplete the extracellular pool of the amino acid. As a consequence, this influences the behavior of MSCs in terms of either cytokine\/chemokine secretion or differentiation potential. Additionally, a direct nutritional interaction exists between MSCs and immune cells. In particular, selected subpopulations of lymphocytes are dependent upon selected amino acids, such as arginine and tryptophan, for full differentiation and competence. This review describes and discusses the nutritional interactions existing in the neoplastic bone marrow niche between MSCs and other cell types, with a particular emphasis on cancer cells and immune cells. These relationships are discussed in the perspective of potential novel therapeutic strategies based on the interference on amino acid metabolism or intercellular fluxes.<\/jats:p>","DOI":"10.3389\/fcell.2021.714755","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T05:44:36Z","timestamp":1625031876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["The Role of Amino Acids in the Crosstalk Between Mesenchymal Stromal Cells and Neoplastic Cells in the Hematopoietic Niche"],"prefix":"10.3389","volume":"9","author":[{"given":"Martina","family":"Chiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Taurino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano G.","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ovidio","family":"Bussolati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1182\/blood-2004-04-1559","article-title":"Human mesenchymal stem cells modulate allogeneic immune cell responses.","volume":"105","author":"Aggarwal","year":"2005","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/jso.24490","article-title":"Arginine-Dual roles as an onconutrient and immunonutrient.","volume":"115","author":"Albaugh","year":"2017","journal-title":"J. Surg. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"4244","DOI":"10.1182\/blood-2005-06-2597","article-title":"Up-regulation of asparagine synthetase expression is not linked to the clinical response L-asparaginase in pediatric acute lymphoblastic leukemia.","volume":"107","author":"Appel","year":"2006","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine Pathway of Tryptophan Metabolism: regulatory and Functional Aspects.","volume":"10","author":"Badawy","year":"2017","journal-title":"Int. J. Tryptophan. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1182\/blood-2016-01-690743","article-title":"Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target.","volume":"128","author":"Bolzoni","year":"2016","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nri1668","article-title":"Regulation of immune responses by L-arginine metabolism.","volume":"5","author":"Bronte","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"B7","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1200\/JCO.2006.07.7792","article-title":"Obesity and outcome in pediatric acute lymphoblastic leukemia.","volume":"25","author":"Butturini","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1096\/fasebj.31.1_supplement.809.8","article-title":"Autophagy and Glutamine Synthetase Induction Sustain ALL Blast Resistance to L-Asparaginase in Human Bone Marrow Mesenchymal Stromal Cells.","volume":"31","author":"Chiu","year":"2017","journal-title":"FASEB J."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051899","article-title":"Functional Consequences of Low Activity of Transport System A for Neutral Amino Acids in Human Bone Marrow Mesenchymal Stem.","volume":"21","author":"Chiu","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113267","article-title":"Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability.","volume":"12","author":"Chiu","year":"","journal-title":"Cancers"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01480","article-title":"Asparagine Synthetase in Cancer: beyond Acute Lymphoblastic Leukemia.","volume":"9","author":"Chiu","year":"2019","journal-title":"Front. Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/nm.4232","article-title":"Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth.","volume":"23","author":"Cramer","year":"2017","journal-title":"Nat. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1002\/ijc.31170","article-title":"The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated-recombinant arginase I BCT-100.","volume":"142","author":"De Santo","year":"","journal-title":"Int. J. Cancer"},{"key":"B14","article-title":"Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma.","volume":"11","author":"De Santo","year":"","journal-title":"J. Hematol. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1038\/2061369a0","article-title":"Interconversion of cystine and cysteine induced by x-rays.","volume":"206","author":"Dewey","year":"1965","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s12185-014-1509-y","article-title":"Expression levels of ASNS in mesenchymal stromal cells in childhood acute lymphoblastic leukemia.","volume":"99","author":"Dimitriou","year":"2014","journal-title":"Int. J. Hematol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1073\/pnas.56.1.156","article-title":"The synthesis of homocystine, cystathionine, and cystine by cultured diploid and heteroploid human cells.","volume":"56","author":"Eagle","year":"1966","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2998","DOI":"10.1158\/0008-5472.can-12-4402","article-title":"Adipocytes cause leukemia cell resistance to L-asparaginase via release of glutamine.","volume":"73","author":"Ehsanipour","year":"2013","journal-title":"Cancer Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.exphem.2013.12.001","article-title":"Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations.","volume":"42","author":"Emadi","year":"2014","journal-title":"Exp. Hematol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-01080-6","article-title":"Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia.","volume":"4","author":"Emadi","year":"2020","journal-title":"Leukemia"},{"key":"B21","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s00280-017-3459-6","article-title":"Asparaginase Erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed\/refractory acute myeloid leukemia.","volume":"81","author":"Emadi","year":"2018","journal-title":"Cancer Chemother. Pharmacol."},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-017-0039-2","article-title":"Del11q-positive CLL lymphocytes exhibit altered glutamine metabolism and differential response to GLS1 and glucose metabolism inhibition.","volume":"8","author":"Galicia-Vazquez","year":"2018","journal-title":"Blood Cancer J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1002\/ijc.30265","article-title":"Tumor-associated mesenchymal stem cells inhibit naive T cell expansion by blocking cysteine export from dendritic cells.","volume":"139","author":"Ghosh","year":"2016","journal-title":"Int. J. Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1080\/14728222.2017.1279148","article-title":"The potential of inhibiting glutamine uptake as a therapeutic target for multiple myeloma.","volume":"21","author":"Giuliani","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"B25","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/0008-8749(90)90184-s","article-title":"Macrophages regulate intracellular glutathione levels of lymphocytes. Evidence for an immunoregulatory role of cysteine.","volume":"129","author":"Gmunder","year":"1990","journal-title":"Cell. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/j.1432-1033.1991.tb16263.x","article-title":"Low membrane transport activity for cystine in resting and mitogenically stimulated human lymphocyte preparations and human T cell clones.","volume":"201","author":"Gmunder","year":"1991","journal-title":"Eur. J. Biochem."},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.1186\/s40170-020-00235-4","article-title":"In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells.","volume":"8","author":"Gonsalves","year":"2020","journal-title":"Cancer Metab."},{"key":"B28","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.94543","article-title":"Glutamine-derived 2-hydroxyglutarate is associated with disease progression in plasma cell malignancies.","volume":"3","author":"Gonsalves","year":"2018","journal-title":"JCI Insight"},{"key":"B29","doi-asserted-by":"publisher","first-page":"5214","DOI":"10.1182\/blood-2009-12-258822","article-title":"Pegylated arginase I: a potential therapeutic approach in T-ALL.","volume":"115","author":"Hernandez","year":"2010","journal-title":"Blood"},{"key":"B30","article-title":"Coordination of asparagine uptake and asparagine synthetase expression modulates CD8+ T cell activation.","volume":"10","author":"Hope","year":"2021","journal-title":"JCI Insight"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.15252\/embj.201695518","article-title":"Role of glutamine and interlinked asparagine metabolism in vessel formation.","volume":"36","author":"Huang","year":"2017","journal-title":"EMBO J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1172\/jci30235","article-title":"Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase.","volume":"117","author":"Iwamoto","year":"2007","journal-title":"J. Clin. Invest."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1182\/blood-2015-01-621870","article-title":"Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition.","volume":"126","author":"Jacque","year":"2015","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1158\/1078-0432.ccr-18-2740","article-title":"Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors.","volume":"25","author":"Jung","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/0006-291x(79)92110-7","article-title":"Cysteine as a system-specific substrate for transport system ASC in rat hepatocytes.","volume":"88","author":"Kilberg","year":"1979","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/s0005-2736(01)00338-8","article-title":"Human cystine\/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells.","volume":"1512","author":"Kim","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"B37","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.clml.2018.12.005","article-title":"A Phase II Study to Determine the Safety and Efficacy of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase (IDO) Enzyme INCB024360 in Patients with Myelodysplastic Syndromes.","volume":"19","author":"Komrokji","year":"2019","journal-title":"Clin. Lymphoma. Myeloma. Leuk."},{"key":"B38","doi-asserted-by":"crossref","DOI":"10.1186\/2162-3619-2-11","article-title":"Vincristine could partly suppress stromal support to T-ALL blasts during pegylated arginase I treatment.","volume":"2","author":"Kwong-Lam","year":"2013","journal-title":"Exp. Hematol. Oncol."},{"key":"B39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/nyas.13102","article-title":"Isolation and characterization of primary bone marrow mesenchymal stromal cells.","volume":"1370","author":"Li","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1080\/10245332.2017.1333245","article-title":"Interferon-gamma mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro.","volume":"23","author":"Liang","year":"2018","journal-title":"Hematology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1158\/0008-5472.can-13-1656","article-title":"Mesenchymal stem cells use IDO to regulate immunity in tumor microenvironment.","volume":"74","author":"Ling","year":"2014","journal-title":"Cancer Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/s1470-2045(19)30274-8","article-title":"Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301\/KEYNOTE-252): a phase 3, randomised, double-blind study.","volume":"20","author":"Long","year":"2019","journal-title":"Lancet Oncol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.canlet.2019.09.011","article-title":"Dysregulation of glutaminase and glutamine synthetase in cancer.","volume":"467","author":"Mates","year":"2019","journal-title":"Cancer Lett."},{"key":"B44","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/j.1600-065x.2012.01149.x","article-title":"Amino acid catabolism: a pivotal regulator of innate and adaptive immunity.","volume":"249","author":"McGaha","year":"2012","journal-title":"Immunol. Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4619","DOI":"10.1182\/blood-2003-11-3909","article-title":"Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation.","volume":"103","author":"Meisel","year":"2004","journal-title":"Blood"},{"key":"B46","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201911210","article-title":"Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages.","volume":"12","author":"Menga","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/leu.2012.247","article-title":"Anti-leukemic mechanisms of pegylated arginase I in acute lymphoblastic T-cell leukemia.","volume":"27","author":"Morrow","year":"2013","journal-title":"Leukemia"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1126\/science.281.5380.1191","article-title":"Prevention of allogeneic fetal rejection by tryptophan catabolism.","volume":"281","author":"Munn","year":"1998","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1182\/blood-2013-01-480129","article-title":"Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment.","volume":"122","author":"Mussai","year":"2013","journal-title":"Blood"},{"key":"B50","doi-asserted-by":"publisher","first-page":"19961","DOI":"10.1073\/pnas.1014465107","article-title":"Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism.","volume":"107","author":"Nguyen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1002\/1878-0261.12877","article-title":"Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia.","volume":"15","author":"Nguyen","year":"2021","journal-title":"Mol. Oncol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/s42255-019-0039-6","article-title":"Critical role of ASCT2-mediated amino acid metabolism in promoting leukaemia development and progression.","volume":"1","author":"Ni","year":"2019","journal-title":"Nat. Metab."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1016\/j.celrep.2017.07.054","article-title":"Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis.","volume":"20","author":"Palmieri","year":"2017","journal-title":"Cell. Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.leukres.2015.04.008","article-title":"Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines.","volume":"39","author":"Parmentier","year":"2015","journal-title":"Leuk. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"5435","DOI":"10.1158\/0008-5472.can-12-0569","article-title":"Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion.","volume":"72","author":"Platten","year":"2012","journal-title":"Cancer Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1007\/s10637-020-00950-1","article-title":"A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma.","volume":"38","author":"Reardon","year":"2020","journal-title":"Invest. New Drugs"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1182\/blood-2006-06-031856","article-title":"L-arginine availability regulates T-lymphocyte cell-cycle progression.","volume":"109","author":"Rodriguez","year":"2007","journal-title":"Blood"},{"key":"B58","article-title":"Biphasic regulation of glutamine consumption by WNT during osteoblast differentiation.","volume":"134","author":"Shen","year":"2021","journal-title":"J. Cell. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"4312","DOI":"10.1182\/bloodadvances.2020001639","article-title":"Amino acid depletion triggered by L-asparaginase sensitizes MM cells to carfilzomib by inducing mitochondria ROS-mediated cell death.","volume":"4","author":"Soncini","year":"2020","journal-title":"Blood Adv."},{"key":"B60","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/0145-2126(90)90184-b","article-title":"Elevated argininosuccinate synthetase activity in adult T leukemia cell lines.","volume":"14","author":"Sugimura","year":"1990","journal-title":"Leuk Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1182\/blood.2019001034","article-title":"Amino acid metabolism in hematologic malignancies and the era of targeted therapy.","volume":"134","author":"Tabe","year":"2019","journal-title":"Blood"},{"key":"B62","doi-asserted-by":"publisher","first-page":"35863","DOI":"10.18632\/oncotarget.16262","article-title":"Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells.","volume":"8","author":"Thompson","year":"2017","journal-title":"Oncotarget"},{"key":"B63","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cmet.2020.07.009","article-title":"Induction of a Timed Metabolic Collapse to Overcome Cancer Chemoresistance.","volume":"32","author":"van Gastel","year":"2020","journal-title":"Cell. Metab."},{"key":"B64","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/s41416-019-0620-5","article-title":"New aspects of amino acid metabolism in cancer.","volume":"122","author":"Vettore","year":"2020","journal-title":"Br. J. Cancer"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.651687","article-title":"Investigating the Role of Indoleamine 2,3-Dioxygenase in Acute Myeloid Leukemia: a Systematic Review.","volume":"12","author":"Wells","year":"2021","journal-title":"Front. Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1182\/blood-2013-03-493163","article-title":"Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia.","volume":"122","author":"Willems","year":"2013","journal-title":"Blood"},{"key":"B67","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41556-020-00615-4","article-title":"Asparagine enhances LCK signalling to potentiate CD8(+) T-cell activation and anti-tumour responses.","volume":"23","author":"Wu","year":"2021","journal-title":"Nat. Cell. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s10637-014-0200-8","article-title":"Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.","volume":"33","author":"Yau","year":"2015","journal-title":"Invest. New. Drugs"},{"key":"B69","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.cmet.2019.01.016","article-title":"Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells.","volume":"29","author":"Yu","year":"2019","journal-title":"Cell. Metab."},{"key":"B70","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cellimm.2005.01.004","article-title":"L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes.","volume":"232","author":"Zea","year":"2004","journal-title":"Cell. Immunol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/ncb2432","article-title":"Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia.","volume":"14","author":"Zhang","year":"2012","journal-title":"Nat. Cell. Biol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.714755\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T23:42:47Z","timestamp":1725320567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.714755\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":71,"alternative-id":["10.3389\/fcell.2021.714755"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.714755","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,30]]},"article-number":"714755"}}