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 hematopoiesi...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 manners.Other than BM,extramedullary hematopoiesis is discovered in various pathophysiological settings.However,whether tumors can contribute to hematopoiesis is completely unknown.Accumulating evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other cells.Here,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate hematopoiesis.Methods:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived pericytes.Genetic tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in vivo.Fluorescence-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological studies.The 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 immunohistochemistry.To investigate BM function in tumor erythropoiesis,BM transplantation mouse models were employed.Results: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 lineage.PDGF-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates erythropoiesis.FACS analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived subpopulation of hematopoietic cells.Single-cell sequencing and colony formation assays validated the fact that,upon PDGF-B stimulation,NG2+cells isolated from tumors acted as erythroblast progenitor cells,which were distinctive from the canonical BM hematopoietic stem cells.Conclusions:Our data provide a new concept of hematopoiesis within tumor tissues and novel mechanistic insights into perivascular localized cell-derived erythroid cells within TME.Targeting tumor hematopoiesis is a novel therapeutic concept for treating various cancers that may have profound impacts on cancer therapy.展开更多
The reduction of CO_(2)into high value-added chemicals and fuels by a photocatalytic technology can relieve energy shortages and the environmental problems caused by greenhouse effects.In the current work,an amino-fun...The reduction of CO_(2)into high value-added chemicals and fuels by a photocatalytic technology can relieve energy shortages and the environmental problems caused by greenhouse effects.In the current work,an amino-functionalized zirconium metal organic framework(Zr-MOF)was covalently modified with different functional groups via the condensation of Zr-MOF with 2-pyridinecarboxaldehyde(PA),salicylaldehyde(SA),benzaldehyde(BA),and trifluoroacetic acid(TA),named Zr-MOF-X(X=PA,SA,BA,and TA),respectively,through the post-synthesis modification.Compared with Zr-MOF and Zr-MOF-TA,the introduction of PA,SA,or BA into the framework of Zr-MOF can not only enhance the visible-light harvesting and CO_(2)capture,but also accelerate the photogenerated charge separation and transfer,thereby improving the photocatalytic ability of Zr-MOF for CO_(2)reduction.These results indicate that the modification of Zr-MOF with electron-donating groups can promote the photocatalytic CO_(2)reduction.Therefore,the current work provides an instructive approach to improve the photocatalytic efficiency of CO_(2)reduction through the covalent modification of MOFs.展开更多
基金CAMS Innovation Fund for Medical Sciences(2021‐I2M‐1‐017),the National Natural Science Foundation of China(81970107),State Key Laboratory of Experimental Hematology Research Grant(Z22‐02)和Tianjin“131”Science Fund for Creative Research Groups(2021)基金支持Yihai Cao获得the Swed is h Research Counc i l(2016‐02215,2019‐01502,2020‐06121,2021‐06122),National Key R&D Program of China(2020YFC0846600)+6 种基金the Hong Kong Centre for Cerebro‐cardiovascular Health Engineering,the Swedish Cancer Foundation(200734PjF),the Swedish Children's Cancer Foundation(PR2018‐0107)the Strategic Research Areas(SFO)‐Stem Cell and Regenerative Medicine Foundation,the Karolinska Institute Foundation(2020‐02080)the Karolinska Institute distinguished professor award,and the Karolinska Institute Foundation(2020‐02588)基金支持Kayoko Hosaka获得the Karolinska Institute Foundation基金支持Takahiro Seki获得the Scandinavia‐Japan Sasakawa Foundation基金支持Xu Jing获得the National Natural Science Foundation of China(81801163)and Doctor Fund of Shandong Natural Science Foundation(ZR201807060846)基金支持Masahito Yoshihara获得the Japan Society for the Promotion of Science(JSPS)Overseas Research Fellowships基金支持。
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-017National Natural Science Foundation of China,Grant/Award Number:81970107+12 种基金State Key Laboratory of Experimental Hematology Research,Grant/Award Number:Z22-02Tianjin“131”Science Fund for Creative Research Groups,Grant/Award Number:2021Swedish Research Council,Grant/Award Numbers:2016-02215,2019-01502,2020-06121,2021-06122National Key R&D Program of China,Grant/Award Number:2020YFC0846600Hong Kong Centre for Cerebro-cardiovascular Health EngineeringSwedish Cancer Foundation,Grant/Award Number:200734PjFSwedish Children’s Cancer Foundation,Grant/Award Number:PR2018-0107Strategic Research Areas(SFO)-Stem Cell and Regenerative Medicine FoundationKarolinska Institute distinguished professor awardKarolinska Institute FoundationScandinavia-Japan Sasakawa Foundation,Grant/Award Number:81801163Doctor Fund of Shandong Natural Science Foundation,Grant/Award Number:ZR201807060846Japan Society for the Promotion of Science(JSPS)Overseas Research Fellowships。
文摘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 manners.Other than BM,extramedullary hematopoiesis is discovered in various pathophysiological settings.However,whether tumors can contribute to hematopoiesis is completely unknown.Accumulating evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other cells.Here,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate hematopoiesis.Methods:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived pericytes.Genetic tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in vivo.Fluorescence-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological studies.The 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 immunohistochemistry.To investigate BM function in tumor erythropoiesis,BM transplantation mouse models were employed.Results: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 lineage.PDGF-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates erythropoiesis.FACS analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived subpopulation of hematopoietic cells.Single-cell sequencing and colony formation assays validated the fact that,upon PDGF-B stimulation,NG2+cells isolated from tumors acted as erythroblast progenitor cells,which were distinctive from the canonical BM hematopoietic stem cells.Conclusions:Our data provide a new concept of hematopoiesis within tumor tissues and novel mechanistic insights into perivascular localized cell-derived erythroid cells within TME.Targeting tumor hematopoiesis is a novel therapeutic concept for treating various cancers that may have profound impacts on cancer therapy.
基金We gratefully acknowledge financial support from the Zhejiang Provincial Key R&D Project(No.2019C03118)the Programme of Introducing Talents of Discipline to Universities(No.D17008).
文摘The reduction of CO_(2)into high value-added chemicals and fuels by a photocatalytic technology can relieve energy shortages and the environmental problems caused by greenhouse effects.In the current work,an amino-functionalized zirconium metal organic framework(Zr-MOF)was covalently modified with different functional groups via the condensation of Zr-MOF with 2-pyridinecarboxaldehyde(PA),salicylaldehyde(SA),benzaldehyde(BA),and trifluoroacetic acid(TA),named Zr-MOF-X(X=PA,SA,BA,and TA),respectively,through the post-synthesis modification.Compared with Zr-MOF and Zr-MOF-TA,the introduction of PA,SA,or BA into the framework of Zr-MOF can not only enhance the visible-light harvesting and CO_(2)capture,but also accelerate the photogenerated charge separation and transfer,thereby improving the photocatalytic ability of Zr-MOF for CO_(2)reduction.These results indicate that the modification of Zr-MOF with electron-donating groups can promote the photocatalytic CO_(2)reduction.Therefore,the current work provides an instructive approach to improve the photocatalytic efficiency of CO_(2)reduction through the covalent modification of MOFs.