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perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

Cancer Communications 2023年第6期43卷 637-660页

作者： Kayoko Hosaka Chenchen Wang Shiyue Zhang Xue Lv Takahiro Seki Yin Zhang Xu Jing Jieyu Wu Qiqiao Du Xingkang He Yulong Fan Xuan Li Makoto Kondo Masahito Yoshihara Hong Qian Lihong Shi Ping Zhu Yuanfu Xu Yunlong Yang Tao Cheng Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinP.R.China Tianjin Institutes of Health Science TianjinP.R.China School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China Center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden Department of cellular and Genetic Medicine School of Basic Medical SciencesFudan UniversityShanghaiP.R.China

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated *** than BM,extramedullary hematopoiesis is discovered in various pathophysiological ***,whether tumors can contribute to hematopoiesis is completely *** evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other ***,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate ***:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived *** tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in ***-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological *** production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and *** investigate BM function in tumor erythropoiesis,BM transplantation mouse models were ***:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid ***-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates *** analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived sub

关键词： cancer hematopoiesis PDGF-B perivascular localized cell stem cell tumor vasculature

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