{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:33:05Z","timestamp":1790083985883,"version":"4.0.1"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007163"],"award-info":[{"award-number":["T32AI007163"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37AI049653"],"award-info":[{"award-number":["R37AI049653"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL149954"],"award-info":[{"award-number":["R01HL149954"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL55337"],"award-info":[{"award-number":["R01HL55337"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007338","name":"Foundation for Barnes-Jewish Hospital","doi-asserted-by":"publisher","award":["5130"],"award-info":[{"award-number":["5130"]}],"id":[{"id":"10.13039\/100007338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1\u03b1 and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, respectively. IL-1\u03b1 induced TNF\u03b1 expression in splenic HSPCs, which then activated splenic niche activity, while LIF induced proliferation of splenic niche cells. IL-1\u03b1 and LIF display cooperative effects in activating EMH and are both up-regulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.<\/jats:p>","DOI":"10.1371\/journal.pbio.3001746","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T17:29:44Z","timestamp":1683134984000},"page":"e3001746","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Tumor-derived interleukin-1\u03b1 and leukemia inhibitory factor promote extramedullary hematopoiesis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-2659","authenticated-orcid":true,"given":"Derek A. G.","family":"Barisas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf Ul","family":"Kabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Krchma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minseo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd H.","family":"Zinselmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyunghee","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"pbio.3001746.ref001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2147\/JBM.S7224","article-title":"Homeostatic and pathogenic extramedullary hematopoiesis","volume":"1","author":"CH Kim","year":"2010","journal-title":"J Blood Med"},{"issue":"2","key":"pbio.3001746.ref002","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.immuni.2019.01.019","article-title":"Emerging principles in myelopoiesis at homeostasis and during infection and inflammation","volume":"50","author":"JL Schultze","year":"2019","journal-title":"Immunity"},{"key":"pbio.3001746.ref003","first-page":"2790","article-title":"Contribution of extramedullary hematopoiesis to atherosclerosis. The spleen as a neglected hub of inflammatory cells","author":"V Fern\u00e1ndez-Garc\u00eda","year":"2020","journal-title":"Front Immunol"},{"issue":"12","key":"pbio.3001746.ref004","first-page":"1","article-title":"Extramedullary hematopoiesis in the absence of myeloproliferative neoplasm: Mayo Clinic case series of 309 patients","volume":"8","author":"N Fan","year":"2018","journal-title":"Blood Cancer J"},{"issue":"8","key":"pbio.3001746.ref005","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.exphem.2006.04.004","article-title":"Peripheral blood stem cell mobilization: the CXCR2 ligand GRO\u03b2 rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties","volume":"34","author":"LM Pelus","year":"2006","journal-title":"Exp Hematol"},{"issue":"1\u20132","key":"pbio.3001746.ref006","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cell.2017.11.003","article-title":"Rapid mobilization reveals a highly engraftable hematopoietic stem cell","volume":"172","author":"J Hoggatt","year":"2018","journal-title":"Cell"},{"issue":"7","key":"pbio.3001746.ref007","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1172\/JCI124738","article-title":"Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells","volume":"129","author":"D Karpova","year":"2019","journal-title":"J Clin Invest"},{"key":"pbio.3001746.ref008","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.2147\/CMAR.S161746","article-title":"Extramedullary hematopoiesis secondary to malignant solid tumors: a case report and literature review","volume":"10","author":"Y Bao","year":"2018","journal-title":"Cancer Manag Res"},{"issue":"8","key":"pbio.3001746.ref009","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1172\/JCI97973","article-title":"Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis","volume":"128","author":"C Wu","year":"2018","journal-title":"J Clin Invest"},{"issue":"5","key":"pbio.3001746.ref010","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"V Bronte","year":"2013","journal-title":"Immunity"},{"issue":"7","key":"pbio.3001746.ref011","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1073\/pnas.1113744109","article-title":"Origins of tumor-associated macrophages and neutrophils","volume":"109","author":"V Cortez-Retamozo","year":"2012","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"pbio.3001746.ref012","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1158\/0008-5472.CAN-17-3026","article-title":"T-cell-Secreted TNFalpha Induces Emergency Myelopoiesis and Myeloid-Derived Suppressor Cell Differentiation in Cancer","volume":"79","author":"MF Al Sayed","year":"2019","journal-title":"Cancer Res"},{"issue":"6","key":"pbio.3001746.ref013","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/ncb3346","article-title":"Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal","volume":"18","author":"EM Pietras","year":"2016","journal-title":"Nat Cell Biol"},{"issue":"9","key":"pbio.3001746.ref014","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.4049\/jimmunol.164.9.4783","article-title":"Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis","volume":"164","author":"P Schwarzenberger","year":"2000","journal-title":"J Immunol"},{"issue":"6","key":"pbio.3001746.ref015","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41591-018-0064-0","article-title":"Myeloid cell contributions to cardiovascular health and disease","volume":"24","author":"M. Nahrendorf","year":"2018","journal-title":"Nat Med"},{"issue":"11","key":"pbio.3001746.ref016","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1182\/blood-2011-11-391342","article-title":"Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and primitive progenitor cells","volume":"120","author":"KA Oduro","year":"2012","journal-title":"Blood"},{"issue":"4","key":"pbio.3001746.ref017","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3390\/cancers12040958","article-title":"Neutrophil to lymphocyte ratio as prognostic and predictive factor in breast cancer patients: a systematic review","volume":"12","author":"I Corbeau","year":"2020","journal-title":"Cancer"},{"issue":"1","key":"pbio.3001746.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-75745-8","article-title":"Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer","volume":"10","author":"N Iwai","year":"2020","journal-title":"Sci Rep"},{"key":"pbio.3001746.ref019","first-page":"106","article-title":"Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis","author":"AJ Templeton","year":"2014","journal-title":"J Natl Cancer Inst"},{"issue":"12","key":"pbio.3001746.ref020","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000010144","article-title":"Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in gastric cancer","volume":"97","author":"Y Zhang","year":"2018","journal-title":"Medicine"},{"issue":"8","key":"pbio.3001746.ref021","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41577-020-00490-y","article-title":"Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity","volume":"21","author":"F Veglia","year":"2021","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"pbio.3001746.ref022","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nri.2017.53","article-title":"Adult haematopoietic stem cell niches","volume":"17","author":"GM Crane","year":"2017","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"pbio.3001746.ref023","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.immuni.2018.03.024","article-title":"Niches for hematopoietic stem cells and their progeny","volume":"48","author":"Q Wei","year":"2018","journal-title":"Immunity"},{"issue":"4","key":"pbio.3001746.ref024","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2184.1978.tb00806.x","article-title":"Dissecting the Hematopoietic Microenvironment: III. EVIDENCE FOR A POSITIVE SHORT RANGE STIMULUS FOR CELLULAR PROLIFERATION","volume":"11","author":"N. Wolf","year":"1978","journal-title":"Cell Prolif"},{"issue":"2","key":"pbio.3001746.ref025","first-page":"174","article-title":"Sl\/Sld hematopoietic progenitors are deficient in situ","volume":"22","author":"J. Barker","year":"1994","journal-title":"Exp Hematol"},{"issue":"6","key":"pbio.3001746.ref026","first-page":"542","article-title":"Early transplantation to a normal microenvironment prevents the development of Steel hematopoietic stem cell defects","volume":"25","author":"J. Barker","year":"1997","journal-title":"Exp Hematol"},{"issue":"1","key":"pbio.3001746.ref027","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1182\/blood-2004-09-3417","article-title":"VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin","volume":"106","author":"T Ulyanova","year":"2005","journal-title":"Blood"},{"issue":"6","key":"pbio.3001746.ref028","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.immuni.2006.10.016","article-title":"Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches","volume":"25","author":"T Sugiyama","year":"2006","journal-title":"Immunity"},{"issue":"7382","key":"pbio.3001746.ref029","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature10783","article-title":"Endothelial and perivascular cells maintain haematopoietic stem cells","volume":"481","author":"L Ding","year":"2012","journal-title":"Nature"},{"issue":"7440","key":"pbio.3001746.ref030","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11885","article-title":"Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches","volume":"495","author":"L Ding","year":"2013","journal-title":"Nature"},{"issue":"7308","key":"pbio.3001746.ref031","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nature09262","article-title":"Mesenchymal and haematopoietic stem cells form a unique bone marrow niche","volume":"466","author":"S M\u00e9ndez-Ferrer","year":"2010","journal-title":"Nature"},{"issue":"5","key":"pbio.3001746.ref032","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.celrep.2013.03.041","article-title":"Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion","volume":"3","author":"J Isern","year":"2013","journal-title":"Cell Rep"},{"issue":"3","key":"pbio.3001746.ref033","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.immuni.2010.08.017","article-title":"The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche","volume":"33","author":"Y Omatsu","year":"2010","journal-title":"Immunity"},{"issue":"7","key":"pbio.3001746.ref034","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1084\/jem.20122252","article-title":"PDGFR\u03b1 and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion","volume":"210","author":"S Pinho","year":"2013","journal-title":"J Exp Med"},{"issue":"12","key":"pbio.3001746.ref035","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1038\/nprot.2012.125","article-title":"Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-\u03b1","volume":"7","author":"DD Houlihan","year":"2012","journal-title":"Nat Protoc"},{"issue":"7727","key":"pbio.3001746.ref036","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41586-018-0590-4","article-title":"Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris","volume":"562","author":"TM Consortium","year":"2018","journal-title":"Nature"},{"issue":"3","key":"pbio.3001746.ref037","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1159\/000129013","article-title":"Phenotypic characterization of mesenchymal stem cells from various tissues","volume":"35","author":"MT Rojewski","year":"2008","journal-title":"Transfus Med Hemother"},{"issue":"7579","key":"pbio.3001746.ref038","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature15530","article-title":"A perisinusoidal niche for extramedullary haematopoiesis in the spleen","volume":"527","author":"CN Inra","year":"2015","journal-title":"Nature"},{"issue":"7","key":"pbio.3001746.ref039","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.cell.2005.05.026","article-title":"SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells","volume":"121","author":"MJ Kiel","year":"2005","journal-title":"Cell"},{"issue":"3","key":"pbio.3001746.ref040","first-page":"954","article-title":"Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease","volume":"12","author":"CT Guy","year":"1992","journal-title":"Mol Cell Biol"},{"issue":"1","key":"pbio.3001746.ref041","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-03600-6","article-title":"Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance","volume":"9","author":"MA Meyer","year":"2018","journal-title":"Nat Commun"},{"issue":"1","key":"pbio.3001746.ref042","first-page":"38","article-title":"Studies in a Tumor Spectrum: III. The Effect of Phosphoramides on the Growth of a Variety of Mouse and Rat Tumors","volume":"15","author":"K Sugiura","year":"1955","journal-title":"Cancer Res"},{"issue":"4","key":"pbio.3001746.ref043","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.cell.2020.07.013","article-title":"TREM2 modulation remodels the tumor myeloid landscape enhancing anti-PD-1 immunotherapy","volume":"182","author":"M Molgora","year":"2020","journal-title":"Cell"},{"issue":"6832","key":"pbio.3001746.ref044","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/35074122","article-title":"IFN\u03b3 and lymphocytes prevent primary tumour development and shape tumour immunogenicity","volume":"410","author":"V Shankaran","year":"2001","journal-title":"Nature"},{"issue":"2","key":"pbio.3001746.ref045","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/jcp.1041520207","article-title":"Interleukin-1\u03b2 induction of TNF-\u03b1 gene expression: Involvement of protein kinase C","volume":"152","author":"JR Bethea","year":"1992","journal-title":"J Cell Physiol"},{"issue":"3","key":"pbio.3001746.ref046","first-page":"e1287247","article-title":"The Interleukin (IL)-1R1 pathway is a critical negative regulator of PyMT-mediated mammary tumorigenesis and pulmonary metastasis","volume":"6","author":"M Dagenais","year":"2017","journal-title":"Onco Targets Ther"},{"issue":"14","key":"pbio.3001746.ref047","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1182\/blood-2016-11-752923","article-title":"Granulocyte colony-stimulating factor mobilizes dormant hematopoietic stem cells without proliferation in mice","volume":"129","author":"JM Bernitz","year":"2017","journal-title":"Blood"},{"issue":"3","key":"pbio.3001746.ref048","doi-asserted-by":"crossref","first-page":"477","DOI":"10.3390\/cancers13030477","article-title":"Therapeutic strategies for targeting IL-1 in cancer","volume":"13","author":"A Gottschlich","year":"2021","journal-title":"Cancer"},{"issue":"7755","key":"pbio.3001746.ref049","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/s41586-019-1104-8","article-title":"The bone marrow microenvironment at single-cell resolution","volume":"569","author":"AN Tikhonova","year":"2019","journal-title":"Nature"},{"issue":"6427","key":"pbio.3001746.ref050","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/363361a0","article-title":"Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation","volume":"363","author":"J-L Escary","year":"1993","journal-title":"Nature"},{"issue":"5","key":"pbio.3001746.ref051","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cytogfr.2015.07.001","article-title":"Leukemia inhibitory factor (LIF).","volume":"26","author":"NA Nicola","year":"2015","journal-title":"Cytokine Growth Factor Rev"},{"issue":"5","key":"pbio.3001746.ref052","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1242\/dev.121.5.1283","article-title":"Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death","volume":"121","author":"CB Ware","year":"1995","journal-title":"Development"},{"issue":"20","key":"pbio.3001746.ref053","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1182\/blood-2008-12-196311","article-title":"Defects in osteoblast function but no changes in long-term repopulating potential of hematopoietic stem cells in a mouse chronic inflammatory arthritis model","volume":"114","author":"YD Ma","year":"2009","journal-title":"Blood"},{"issue":"6","key":"pbio.3001746.ref054","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1523\/JNEUROSCI.3803-11.2012","article-title":"Exogenous leukemia inhibitory factor stimulates oligodendrocyte progenitor cell proliferation and enhances hippocampal remyelination","volume":"32","author":"BE Deverman","year":"2012","journal-title":"J Neurosci"},{"issue":"12","key":"pbio.3001746.ref055","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/jbmr.5650061203","article-title":"Regulation of osteoblast proliferation by leukemia inhibitory factor","volume":"6","author":"C Lowe","year":"1991","journal-title":"J Bone Miner Res"},{"issue":"10","key":"pbio.3001746.ref056","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The cancer genome atlas pan-cancer analysis project","volume":"45","author":"K Chang","year":"2013","journal-title":"Nat Genet"},{"issue":"6","key":"pbio.3001746.ref057","first-page":"E566","article-title":"Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils","volume":"112","author":"A-J Casbon","year":"2015","journal-title":"Proc Natl Acad Sci"},{"issue":"7","key":"pbio.3001746.ref058","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/rheumatology\/keq031","article-title":"Transmembrane TNF-\u03b1: structure, function and interaction with anti-TNF agents","volume":"49","author":"T Horiuchi","year":"2010","journal-title":"Rheumatology"},{"issue":"5","key":"pbio.3001746.ref059","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1158\/0008-5472.CAN-06-1021","article-title":"Leukemia inhibitory factor: a newly identified metastatic factor in rhabdomyosarcomas","volume":"67","author":"M Wysoczynski","year":"2007","journal-title":"Cancer Res"},{"issue":"1","key":"pbio.3001746.ref060","first-page":"1","article-title":"LIF negatively regulates tumour-suppressor p53 through Stat3\/ID1\/MDM2 in colorectal cancers","volume":"5","author":"H Yu","year":"2014","journal-title":"Nat Commun"},{"issue":"3","key":"pbio.3001746.ref061","doi-asserted-by":"crossref","first-page":"788","DOI":"10.18632\/oncotarget.1772","article-title":"LIF promotes tumorigenesis and metastasis of breast cancer through the AKT-mTOR pathway","volume":"5","author":"X Li","year":"2014","journal-title":"Oncotarget"},{"issue":"5","key":"pbio.3001746.ref062","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/j.celrep.2014.04.036","article-title":"LIF mediates proinvasive activation of stromal fibroblasts in cancer","volume":"7","author":"J Albrengues","year":"2014","journal-title":"Cell Rep"},{"issue":"1","key":"pbio.3001746.ref063","first-page":"1","article-title":"Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer","volume":"10","author":"M-T Wang","year":"2019","journal-title":"Nat Commun"},{"issue":"7754","key":"pbio.3001746.ref064","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41586-019-1130-6","article-title":"Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring","volume":"569","author":"Y Shi","year":"2019","journal-title":"Nature"},{"issue":"1","key":"pbio.3001746.ref065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-10369-9","article-title":"LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy","volume":"10","author":"M Pascual-Garc\u00eda","year":"2019","journal-title":"Nat Commun"},{"issue":"3","key":"pbio.3001746.ref066","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","article-title":"A framework for advancing our understanding of cancer-associated fibroblasts","volume":"20","author":"E Sahai","year":"2020","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"pbio.3001746.ref067","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.ccell.2021.04.014","article-title":"Conserved pan-cancer microenvironment subtypes predict response to immunotherapy","volume":"39","author":"A Bagaev","year":"2021","journal-title":"Cancer Cell"},{"key":"pbio.3001746.ref068","doi-asserted-by":"crossref","first-page":"100896","DOI":"10.1016\/j.xcrm.2022.100896","article-title":"Conserved angio-immune subtypes of the tumor microenvironment predict response to immune checkpoint blockade therapy","author":"M Subramanian","year":"2023","journal-title":"Cell Rep Med"},{"issue":"3","key":"pbio.3001746.ref069","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.stem.2019.05.019","article-title":"TNF-\u03b1 coordinates hematopoietic stem cell survival and myeloid regeneration","volume":"25","author":"M Yamashita","year":"2019","journal-title":"Cell Stem Cell"},{"issue":"12","key":"pbio.3001746.ref070","doi-asserted-by":"crossref","first-page":"108530","DOI":"10.1016\/j.celrep.2020.108530","article-title":"Interferon gamma mediates hematopoietic stem cell activation and niche relocalization through BST2","volume":"33","author":"MA Florez","year":"2020","journal-title":"Cell Rep"},{"issue":"8","key":"pbio.3001746.ref071","first-page":"816","article-title":"Inflammatory signals directly instruct PU. 1 in HSCs via TNF","volume":"133","author":"M Etzrodt","year":"2019","journal-title":"Blood, The Journal of the American Society of. Hematology"},{"issue":"1","key":"pbio.3001746.ref072","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1182\/blood.2021011570","article-title":"IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice","volume":"139","author":"LV Kovtonyuk","year":"2022","journal-title":"Blood"},{"issue":"4","key":"pbio.3001746.ref073","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.stem.2014.01.007","article-title":"Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis","volume":"14","author":"JL Zhao","year":"2014","journal-title":"Cell Stem Cell"},{"issue":"6","key":"pbio.3001746.ref074","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1210\/en.2017-00103","article-title":"Tissue-specific ablation of the LIF receptor in the murine uterine epithelium results in implantation failure","volume":"158","author":"J Cheng","year":"2017","journal-title":"Endocrinology"},{"issue":"12","key":"pbio.3001746.ref075","doi-asserted-by":"crossref","first-page":"giaa151","DOI":"10.1093\/gigascience\/giaa151","article-title":"SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data","volume":"9","author":"MD Young","year":"2020","journal-title":"Gigascience"},{"issue":"7","key":"pbio.3001746.ref076","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"T Stuart","year":"2019","journal-title":"Cell"},{"issue":"1","key":"pbio.3001746.ref077","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"C Hafemeister","year":"2019","journal-title":"Genome Biol"},{"issue":"7","key":"pbio.3001746.ref078","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods"},{"issue":"1","key":"pbio.3001746.ref079","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"D Aran","year":"2017","journal-title":"Genome Biol"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3001746","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T17:33:02Z","timestamp":1683135182000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3001746"}},"subtitle":[],"editor":[{"given":"Avinash","family":"Bhandoola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":79,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3001746","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]}}}