The association of neurogenesis and gliogenesis with glioma remains unclear.By conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-O...The association of neurogenesis and gliogenesis with glioma remains unclear.By conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-OPC)-like and radial glia(RG)-like tumors and validated it in a public cohort and TCGA glioma.The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations,and the pri-OPC-like ones were prone to carrying TP53 mutations.Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes,suggesting their distinct immune evasion programs.Furthermore,the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners.Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes.For example,glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes,respectively.Their expression was positively correlated with those of immune checkpoint genes(e.g.,LGALS33)and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells.This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.展开更多
基金supported by talent startup funding from Fudan University(Nos.JIF101017,SXF101012,and JIF101047)Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Project(No.2021ZD0201100 Task 4 and No.2021ZD0201104)from the Ministry of Science and Technology(MOST),China+3 种基金Jinsong Wu was supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJ Lab,and operating grant of Shanghai Brain Bank technical system(No.16JC1420103)Edwin Wang was supported by Alberta Innovates Translational Chair Program in Cancer Genomics,the Natural Sciences and Engineering Research Council of Canada(NSERC,No.RGPIN-2017-04885)Canadian Foundation of Innovation(No.36655).
文摘The association of neurogenesis and gliogenesis with glioma remains unclear.By conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-OPC)-like and radial glia(RG)-like tumors and validated it in a public cohort and TCGA glioma.The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations,and the pri-OPC-like ones were prone to carrying TP53 mutations.Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes,suggesting their distinct immune evasion programs.Furthermore,the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners.Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes.For example,glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes,respectively.Their expression was positively correlated with those of immune checkpoint genes(e.g.,LGALS33)and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells.This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.
