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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell rna-seq analysis

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Frontiers of Medicine 2024年第1期18卷 147-168页

作者： Weiwei Xian Mohammad Asad Shuai Wu Zhixin Bai Fengjiao Li Junfeng Lu Gaoyu Zu Erin Brintnell Hong Chen Ying Mao Guomin Zhou Bo Liao Jinsong Wu Edwin Wang Linya You Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghai200032China Cumming School of Medicine University of CalgaryCalgaryAlbertaT2N 4N1Canada Glioma Surgery Division Department of NeurosurgeryHuashan HospitalFudan UniversityShanghai200040China Department of Pathology Huashan HospitalFudan UniversityShanghai200040China Department of Neurosurgery Huashan HospitalFudan UniversityShanghai200040China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Fudan UniversityShanghai200040China School of Mathematics and Statistics Hainan Normal UniversityHaikou570100China

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.

关键词： single-cell rna-seq glioma radial glia primitive oligodendrocyte precursor cell immune escape

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single-cell rna-seq reveals transcriptional regulatory networks directing the development of mouse maxillary prominence

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Journal of Genetics and Genomics 2023年第9期50卷 676-687页

作者： Jian Sun Yijun Lin Nayoung Ha Jianfei Zhang Weiqi Wang Xudong Wang Qian Bian Department of Oral and Cranio-Maxillofacial Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China Shanghai Institute of Precision Medicine Shanghai 200125China Shanghai Key Laboratory of Reproductive Medicine Shanghai Jiao Tong University School of MedicineShanghai 200025China

During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell rna-seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.

关键词： Craniofacial development single-cell rna-seq Maxillary prominences Gene regulatory network Transcription factor

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single-cell rna-seq of Lotus japonicus provide insights into identification and function of root cell types of legume

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Journal of Integrative Plant Biology 2023年第5期65卷 1147-1152页

作者： Zhanmin Sun Sanjie Jiang Dan Wang Linxia Li Boxin Liu Qifan Ran Lizhen Hu Junbo Xiong Yixiong Tang Xiaofeng Gu Yanmin Wu Zhe Liang Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China BGl Genomics Shenzhen 518083China Key Laboratory of Southwest China Wildlife Resources Conservation China West Normal UniversityNanchong 637002China Chongqing Academy of Animal Sciences Chongqing 402460China Institute of Animal and Veterinary Science Jiangxi Academy of Agricultural SciencesNanchang 330200China Hubei Key Laboratory of Animal Embryo and Molecular Breeding Institute of Animal and Veterinary ScienceHubei Academy of Agricultural ScienceWuhan 430072China

The roots of legume plant play a crucial role in nitrogen fixation. However, the transcriptomes of different cell types of legume root and their functions remain largely unknown. Here, we performed single-cell rna sequencing and profiled more than 22,000 single cells from root tips of Lotus japonicus, a model species of legume.We identified seven clusters corresponding to seven major cell types, which were validated by in situ hybridization. Further analysis revealed regulatory programs including phytohormone and nodulation associated with specific cell types, and revealed conserved and diverged features for the cell types. Our results represent the first single-cell resolution transcriptome for legume root tips and a valuable resource for studying the developmental and physiological functions of various cell types in legumes.

关键词： genome legume Lotus japonicus single-cell rna-seq

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single-cell profiling of the pig cecum at various developmental stages

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Zoological Research 2024年第1期45卷 55-68页

作者： Yan-Yuan Xiao Qing Zhang Fei Huang Lin Rao Tian-Xiong Yao Si-Yu Yang Lei Xie Xiao-Xiao Zou Li-Ping Cai Jia-Wen Yang Bin Yang Lu-Sheng Huang National Key Laboratory for Swine Genetic Improvement and Germplasm Innovation Ministry of Science and Technology of ChinaJiangxi Agricultural UniversityNanchangJiangxi 330045China

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell rna sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

关键词： single-cell rna-seq Cecum Bama Xiang pigs Various developmental stages cellular heterogeneity

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Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATACseq and scrna-seq

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Zoological Research 2024年第3期45卷 601-616页

作者： Hai-Quan Wang Xiao-Long Wu Jing Zhang Si-Ting Wang Yong-Juan Sang Kang Li Chao-Fan Yang Fei Sun Chao-Jun Li State Key Laboratory of Reproductive Medicine and Offspring Health Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Medical School Nanjing UniversityNanjingJiangsu 210093China Zhejiang University School of Medicine HangzhouZhejiang 310016China Department of Urology and Andrology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouZhejiang 310000China Model Animal Research Center of Medical School Nanjing UniversityNanjingNanjingJiangsu 210093China Liangzhu Laboratory Zhejiang UniversityHangzhouZhejiang 311121China

Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

关键词： single-cell rna-seq single-cell ATAC-seq Spermatogenesis Meiosis Transcriptional reprogramming cell-cell communication

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single-cell transcriptomic landscape of peripheral blood cells provides insights into adaptation of red-eared sliders(Trachemys scripta elegans)

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Integrative Zoology 2024年第3期19卷 468-479页

作者： Rui GUO Guangwei MA Xiaofei ZHAI Haitao SHI Jichao WANG Ministry of Education Key Laboratory for Ecology of Tropical Islands Key Laboratory of Tropical Animal and Plant Ecology of Hainan ProvinceCollege of Life SciencesHainan Normal UniversityHaikouChina

Red-eared sliders(Trachemys scripta elegans),as one of the 100 most threatening aliens,have stronger immunity than the native species in response to environmental stress.Blood cells are an important component of immunity in the body.However,the blood cell researches of turtle are still in the traditional blood cell classification and morphological structure observation.Furthermore,turtle granulocytes cannot be accurately identified using traditional methods.single-cell rna sequencing techniques have been successfully implemented to study cells based on the mrna expression patterns of each cell.The present study profiled the transcriptomes of peripheral blood cells in red-eared sliders to construct a single-cell transcriptional landscape of the different cell types and explored environmental adaptation mechanism from the perspective of hematology.All 14 transcriptionally distinct clusters(platelets,erythrocytes1,erythrocytes2,CSF1R monocytes,POF1B monocytes,neutrophils,GATA2high basophils,GATA2low basophils,CD4 T cells,CD7 T cells,B cells,ACKR4 cells,serotriflin cells,and ficolin cells)were identified in the peripheral blood cells of the red-eared sliders.In particular,a subtype of erythrocytes(erythrocytes1)that expressed immune signals was identified.Peripheral blood cells were grouped into three lineages:platelet,erythroid/lymphoid,and myeloid cell lineages.Furthermore,based on differentiation trajectory and up-regulated gene expression,ACKR4 cells were newly identified as lymphocytes,and serotriflin and ficolin cells as granulocytes.The single-cell transcriptional atlas of the peripheral blood cells in red-eared sliders provided in the present study will offer a comprehensive transcriptome reference for the exploration of physiological and pathological hematology in this species.

关键词： blood cells single-cell rna-seq Trachemys scripta elegans

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single-cell rna-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

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Frontiers of Medicine 2020年第2期14卷 185-192页

作者： Xin Zou Ke Chen Jiawei Zou Peiyi Han Jie Hao Zeguang Han Key Laboratory of Systems Biomedicine(Ministry of Education) Shanghai Centre for Systems BiomedicineShanghai Jiao Tong UniversityShanghai 200240China Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025China

It has been known that,the novel coronavirus,2019-nCoV,which is considered similar to SARS-CoV,invades human cells via the receptor angiotensin converting enzyme II(ACE2).Moreover,lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection.However,some patients also exhibit non-respiratory symptoms,such as kidney failure,implying that 2019-nCoV could also invade other organs.To construct a risk map of different human organs,we analyzed the single-cell rna sequencing(scrna-seq)datasets derived from major human physiological systems,including the respiratory,cardiovascular,digestive,and urinary systems.Through scrna-seq data analyses,we identified the organs at risk,such as lung,heart,esophagus,kidney,bladder,and ileum,and located specific cell types(i.e.,type II alveolar cells(AT2),myocardial cells,proximal tubule cells of the kidney,ileum and esophagus epithelial cells,and bladder urothelial cells),which are vulnerable to 2019-nCoV infection.Based on the findings,we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection.This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

关键词： 2019-nCoV ACE2 single-cell rna-seq

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Effects of vitrification and cryostorage duration on single-cell rna-seq profiling of vitrified-thawed human metaphase Ⅱ oocytes

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Frontiers of Medicine 2021年第1期15卷 144-154页

作者： Ying Huo Peng Yuan Qingyuan Qin Zhiqiang Yan Liying Yan Ping Liu Rong Li Jie Yan Jie Qiao Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction Beijing 100191China Key Laboratory of Assisted Reproduction Ministry of EducationBeijing 100191China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China National Clinical Research Center of Obstetrics and Gynecology Beijing 100191China

Oocyte cryopreservation is widely used for clinical and social reasons.Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures,but not storage time,can alter the gene expression profiles of frozen oocytes.Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase Ⅱ oocytes remain unknown.Four women(30–32 years old)who had undergone IVF treatment were recruited for this study.rna-seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes(3,3,4,and 3 oocytes were cryostored for 1,2,3,and 12 months)were analyzed at a single-cell resolution.A total of 1987 genes were differentially expressed in the 13 vitrifiedthawed oocytes.However,no differentially expressed genes were found between any two groups among the 1-,2-,3-,and 12-month storage groups.Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development.Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself,suggesting that long-term cryostorage of human oocytes is safe.

关键词： human metaphaseⅡoocyte vitrification cryostorage duration single-cell rna-seq lncrna

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Imputing single-cell rna-seq data by considering cell heterogeneity and prior expression of dropouts

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Journal of Molecular cell Biology 2021年第1期13卷 29-40页

作者： Lihua Zhang Shihua Zhang NCMIS CEMSRCSDSAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100049China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Key Laboratory of Systems Biology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesChinese Academy of SciencesHangzhou 310024China

single-cell rna sequencing(scrna-seq)provides a powerful tool to determine expression patterns of thousands of individual cells.However,the analysis of scrna-seq data remains a computational challenge due to the high technical noise such as the presence of dropout events that lead to a large proportion of zeros for expressed genes.Taking into account the cell heterogeneity and the relationship between dropout rate and expected expression level,we present a cell sub-population based bounded low-rank(PBLR)method to impute the dropouts of scrna-seq data.Through application to both simulated and real scrna-seq datasets,PBLR is shown to be effective in recovering dropout events,and it can dramaimprove the low・dimensional representation and the recovery of gene-gene relationships masked by dropout events compared to several state-of-the-art methods・Moreover,PBLR also detects accurate and robust cell sub-populations automatically,shedding light on its flexibility and generality for scrna-seq data analysis.

关键词： single-cell rna-seq dropout imputation low订ank systems biology

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MR-seq:measuring a single cell's transcriptome repeatedly by rna-seq

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Science Bulletin 2017年第6期62卷 391-398页

作者： Lu Yang Zhaochun Ma Chen Cao Yuhao Zhang Xinglong Wu Raymond Lee Boqiang Hu Lu Wen Hao Ge Yanyi Huang Kaiqin Lao Fuchou Tang Biodynamic Optical Imaging Center School of Life Sciences Peking University Beijing 100871 China Thermo Fisher Scientific.South San Francisco CA 94080 USA Peking-Tsinghua Center for Life Sdences Beijing 100084 China Beijing International Center for Mathematical Research (BICMR) Peking University Beijing 100871 China College of Engineering Peking University Beijing 100871 China China Center for Molecular and Translationai Medicine (CMTM) Beijing 100101 China Beijing Advanced Innovation Center for Cenomics (ICG) Peking University Beijing 100871 China

We described a novel single-cell rna-seq technique called MR-seq(measure a single-cell transcriptome repeatedly),which permits statistically assessing the technical variation and identifying the differentially expressed genes between just two single cells by measuring each single cell twice. We demonstrated that MR-seq gave sensitivity and reproducibility similar to the standard single-cell rna-seq and increased the positive predicate value. Application of MR-seq to early mouse embryos identified hundreds of candidate intra-embryonic heterogeneous genes among mouse 2-,4-and 8-cell stage embryos. MR-seq should be useful for detecting differentially expressed genes among a small number of cells.

关键词： single-cell rna-seq Differentially expressed genes Intra-embryonic heterogeneity Mouse early preimplantation embryos

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