Terrestrial plants can affect the growth and health of adjacent plants via interspecific interaction.Here,we studied the mechanism by which plant root exudates affect the recruitment of the rhizosphere microbiome in a...Terrestrial plants can affect the growth and health of adjacent plants via interspecific interaction.Here,we studied the mechanism by which plant root exudates affect the recruitment of the rhizosphere microbiome in adjacent plants—with implications for plant protection—using a tomato(Solanum lycopersicum)–potatoonion(Allium cepa var.agrogatum)intercropping system.First,we showed that the intercropping system results in a disease-suppressive rhizosphere microbiome that protects tomato plants against Verticillium wilt disease caused by the soilborne pathogen Verticillium dahliae.Second,16S rRNA gene sequencing revealed that intercropping with potatoonion altered the composition of the tomato rhizosphere microbiome by promoting the colonization of specific Bacillus sp.This taxon was isolated and shown to inhibit V.dahliae growth and induce systemic resistance in tomato plants.Third,a belowground segregation experiment found that root exudates mediated the interspecific interaction between potatoonion and tomato.Moreover,experiments using split-root tomato plants found that root exudates from potatoonion,especially taxifolin—a flavonoid compound—stimulate tomato plants to recruit plant-beneficial bacteria,such as Bacillus sp.Lastly,ultra-high-pressure liquid chromatography–mass spectrometry analysis found that taxifolin alters tomato root exudate chemistry;thus,this compound acts indirectly in modulating root colonization by Bacillus sp.Our results revealed that this intercropping system can improve tomato plant fitness by changing rhizosphere microbiome recruitment via the use of signaling chemicals released by root exudates of potatoonion.This study revealed a novel mechanism by which interspecific plant interaction modulates the establishment of a disease-suppressive microbiome,thus opening up new avenues of research for precision plant microbiome manipulations.展开更多
Background and Aims:Collagenβ(1-O)galactosyltransferase 25 domain 1(GLT25D1)is associated with collagen production and glycosylation,and its knockout in mice results in embryonic death.However,its role in liver fibro...Background and Aims:Collagenβ(1-O)galactosyltransferase 25 domain 1(GLT25D1)is associated with collagen production and glycosylation,and its knockout in mice results in embryonic death.However,its role in liver fibrosis remains elusive,particularly in hepatic stellate cells(HSCs),the primary collagen-producing cells associated with liver fibrogenesis.Herein,we aimed to elucidate the role of GLT25D1 in HSCs.Methods:Bile duct ligation(BDL)-induced mouse liver fibrosis models,primary mouse HSCs(mHSCs),and transforming growth factor beta 1(TGF-β1)-stimulated LX-2 human hepatic stellate cells were used in in vivo and in vitro studies.Stable LX-2 cell lines with either GLT25D1 overexpression or knockdown were established using lentiviral transfection.RNA-seq was performed to investigate the genomic differences.HPLCMS/MS were used to identify glycosylation sites.Scanning electronic microscopy(SEM)and second-harmonic generation/two-photon excited fluorescence(SHG/TPEF)were used to image collagen fibril morphology.Results:GLT25D1 expression was upregulated in nonparenchymal cells in human cirrhotic liver tissues.Meanwhile,its knockdown attenuated collagen deposition in BDL-induced mouse liver fibrosis and inhibited mHSC activation.GLT25D1 was overexpressed in activated versus quiescence LX-2 cells and regulated in vitro LX-2 cell activation,including proliferation,contraction,and migration.GLT25D1 also significantly increased liver fibrogenic gene and protein expression.GLT25D1 upregulation promoted HSC activation and enhanced collagen expression through the TGF-β1/SMAD signaling pathway.Mass spectrometry showed that GLT25D1 regulated the glycosylation of collagen in HSCs,affecting the diameter of collagen fibers.Conclusions:Collectively,the upregulation of GLT25D1 in HSCs promoted the progression of liver fibrosis by affecting HSCs activation and collagen stability.展开更多
Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlyi...Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8(HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.展开更多
基金supported by the National Key Research and Development Program(2021YFD1900100,2018YFD1000800)the National Natural Science Foundation of China(32072655,32172652)the China Agriculture Research System of MOF and MARA(CARS-23-B-10).
文摘Terrestrial plants can affect the growth and health of adjacent plants via interspecific interaction.Here,we studied the mechanism by which plant root exudates affect the recruitment of the rhizosphere microbiome in adjacent plants—with implications for plant protection—using a tomato(Solanum lycopersicum)–potatoonion(Allium cepa var.agrogatum)intercropping system.First,we showed that the intercropping system results in a disease-suppressive rhizosphere microbiome that protects tomato plants against Verticillium wilt disease caused by the soilborne pathogen Verticillium dahliae.Second,16S rRNA gene sequencing revealed that intercropping with potatoonion altered the composition of the tomato rhizosphere microbiome by promoting the colonization of specific Bacillus sp.This taxon was isolated and shown to inhibit V.dahliae growth and induce systemic resistance in tomato plants.Third,a belowground segregation experiment found that root exudates mediated the interspecific interaction between potatoonion and tomato.Moreover,experiments using split-root tomato plants found that root exudates from potatoonion,especially taxifolin—a flavonoid compound—stimulate tomato plants to recruit plant-beneficial bacteria,such as Bacillus sp.Lastly,ultra-high-pressure liquid chromatography–mass spectrometry analysis found that taxifolin alters tomato root exudate chemistry;thus,this compound acts indirectly in modulating root colonization by Bacillus sp.Our results revealed that this intercropping system can improve tomato plant fitness by changing rhizosphere microbiome recruitment via the use of signaling chemicals released by root exudates of potatoonion.This study revealed a novel mechanism by which interspecific plant interaction modulates the establishment of a disease-suppressive microbiome,thus opening up new avenues of research for precision plant microbiome manipulations.
基金funded by the National Science Foundation of China [No.82170541]National Science Foundation of China [No.81900549]+4 种基金Natural Science Foundation of Beijing Municipality [No.7202071]The Capital Foundation for Clinical Characteristic Applied Research Projects [No.Z181100001718084]The Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals [No.XXZ0404]The Study on Modernization of Traditional Chinese Medicine [No.2018YFC1705700]Capital Medical University Research Development Fund [No.PYZ20031].
文摘Background and Aims:Collagenβ(1-O)galactosyltransferase 25 domain 1(GLT25D1)is associated with collagen production and glycosylation,and its knockout in mice results in embryonic death.However,its role in liver fibrosis remains elusive,particularly in hepatic stellate cells(HSCs),the primary collagen-producing cells associated with liver fibrogenesis.Herein,we aimed to elucidate the role of GLT25D1 in HSCs.Methods:Bile duct ligation(BDL)-induced mouse liver fibrosis models,primary mouse HSCs(mHSCs),and transforming growth factor beta 1(TGF-β1)-stimulated LX-2 human hepatic stellate cells were used in in vivo and in vitro studies.Stable LX-2 cell lines with either GLT25D1 overexpression or knockdown were established using lentiviral transfection.RNA-seq was performed to investigate the genomic differences.HPLCMS/MS were used to identify glycosylation sites.Scanning electronic microscopy(SEM)and second-harmonic generation/two-photon excited fluorescence(SHG/TPEF)were used to image collagen fibril morphology.Results:GLT25D1 expression was upregulated in nonparenchymal cells in human cirrhotic liver tissues.Meanwhile,its knockdown attenuated collagen deposition in BDL-induced mouse liver fibrosis and inhibited mHSC activation.GLT25D1 was overexpressed in activated versus quiescence LX-2 cells and regulated in vitro LX-2 cell activation,including proliferation,contraction,and migration.GLT25D1 also significantly increased liver fibrogenic gene and protein expression.GLT25D1 upregulation promoted HSC activation and enhanced collagen expression through the TGF-β1/SMAD signaling pathway.Mass spectrometry showed that GLT25D1 regulated the glycosylation of collagen in HSCs,affecting the diameter of collagen fibers.Conclusions:Collectively,the upregulation of GLT25D1 in HSCs promoted the progression of liver fibrosis by affecting HSCs activation and collagen stability.
基金the National Natural Science Foundation of China(31571298).
文摘Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8(HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.