Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at t...Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.展开更多
Every river basin is characterised by an evolutionary history,which may be analysed at different time scales.This study provides a geological and geomorphic history of different river basins of India at different time...Every river basin is characterised by an evolutionary history,which may be analysed at different time scales.This study provides a geological and geomorphic history of different river basins of India at different time scales ranging from millions of years to millennial time scales.The river basins in India are divided into six different groups on the basis of different tectono-climatic settings and geomorphic characteristics.The evolutionary trajectories in the past strongly govern the modern day geomorphic characteristics and processes in a river basin.The basin scale data compiled in this paper highlights the role of geological inheritance and‘landscape memory’in the evolution of river systems of India.展开更多
Background Medullary thyroid cancer(MTC)is a rare neuroendocrine tumor that originates from the parafollicular C cells of thyroid gland.Understanding the fundamental pathophysiology of MTC is essential for clinical ma...Background Medullary thyroid cancer(MTC)is a rare neuroendocrine tumor that originates from the parafollicular C cells of thyroid gland.Understanding the fundamental pathophysiology of MTC is essential for clinical manage-ment.Single-cell RNA sequencing(scRNA-seq)technology is a powerful tool for identifying distinct cell types,offering a new biological foundation for comprehending the MTC ecosystem and developing precise treatment.Methods Formalin fixed and paraffin-embedded(FFPE)samples of primary and adjacent non-cancerous tissues of three MTC cases were collected,and single-cell transcriptome data of MTC were obtained by using scRNA-seq technology.Annotated cell subpopulations were categorized and functionally enriched by principal component analysis,differential gene expression,and cell clustering analysis,to explore the biological process of tumor evolution that may be involved in each cell subpopulation.The copy number variation(CNV)profile was used to distinguish the malignancy of parafollicular thyroid cells,and the evolutionary trajectories of normal cells and tumor cells were revealed by the proposed time series analysis.The highly expressed genes in each cell subpopulation were analyzed by the FindAllMarker function of Seurat software,and verified by immunohistochemistry and fluorescence in situ hybridization.The prognostic value of specific cell subtypes was validated using large-scale public datasets.Results A total of 32,544 cells were obtained from the MTC tissue samples and 11,751 cells from the adjacent non-cancerous samples,which were classified into 7 heterogenous subpopulations by using R package of Seurat mod-ule.Copy number variations(CNVs)were significantly higher in tumor tissues than in adjacent non-tumor samples,predominantly enriched in subtypes C2 and C4.In addition,the pseudo-time for trajectory analysis suggested that the evolution of MTC tumor cells might begin with the C2 subtype,then transition to the early cancer sub-group C3,and further differentiate into four major malignant cell subpopulations C0,C1,C5 and C6.Survival analysis of a thyroid cancer cohort using the TCGA dataset revealed that high expression of genes linked to the C0 subcluster was correlated with poorer overall survival compared to low expression.Immunohistochemical staining showed that MAP3K4 was highly expressed in MTC tissues compared to adjacent non-cancerous tissues.Fluorescence in situ hybridization also confirmed the amplification of these two genes in MTC samples.Conclusions By conducting scRNA-seq on FFPE samples,we mapped the single-cell transcriptome of MTC,uncov-ering the tumor heterogeneity and unique biological features of each cellular subpopulation.The biological roles of identified tumor cell subpopulations such as C0 and C3 subtypes of parafollicular cells suggested the potential to discover new therapeutic targets and biomarkers for MTC,providing valuable insights for future translational and clinical research.展开更多
JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a ...JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a nearly complete genome assembly of JUJUNCAO and reveal that JUJUNCAO is an allopolyploid that originated2.7 million years ago(mya).Its genome consists of two subgenomes,and subgenome A shares high collinear synteny with pearl millet.We also investigated the genome evolution of JUJUNCAO and suggest that the ancestral karyotype of Cenchrus split into the A and B ancestral karyotypes of JUJUNCAO.Comparative transcriptome and DNA methylome analyses revealed functional divergence of homeologous gene pairs between the two subgenomes,which was a further indication of asymmetric DNA methylation.The three types of centromeric repeat in the JUJUNCAO genome(CEN137,CEN148,and CEN156)may have evolved independently within each subgenome,with some introgressions of CEN156 from the B to the A subgenome.We investigated the photosynthetic characteristics of JUJUNCAO,revealing its typical C4 Kranz anatomy and high photosynthetic efficiency.NADP-ME and PEPCK appear to cooperate in the major C4 decarboxylation reaction of JUJUNCAO,which is different from other C4 photosynthetic subtypes and may contribute to its high photosynthetic efficiency and biomass yield.Taken together,our results provide insights into the highly efficient photosynthetic mechanism of JUJUNCAO and provide a valuable reference genome for future genetic and evolutionary studies,as well as genetic improvement of Cenchrus grasses.展开更多
基金supported by National Key Research and Development Program of China(No.2017YFC1308800)Industry-University-Research Innovation Fund in Ministry of Education of the People’s Republic of China(No.2018A01013)。
文摘Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.
基金supported by COFUND fellowship at Durham University,UKSonam was supported by PhD fellowship provided by CSIR-UGC,India(Fellowship No.061320507-23/06/2013(i)EU-V).
文摘Every river basin is characterised by an evolutionary history,which may be analysed at different time scales.This study provides a geological and geomorphic history of different river basins of India at different time scales ranging from millions of years to millennial time scales.The river basins in India are divided into six different groups on the basis of different tectono-climatic settings and geomorphic characteristics.The evolutionary trajectories in the past strongly govern the modern day geomorphic characteristics and processes in a river basin.The basin scale data compiled in this paper highlights the role of geological inheritance and‘landscape memory’in the evolution of river systems of India.
基金supported by Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX1047)Natural Science Foundation of Chongqing(NO.CSTB2023NSCQ-MSX0821)Scientific research project of Chongqing Medical Biotechnology Association(NO.cmba2022kyym-zkxmQ0012).
文摘Background Medullary thyroid cancer(MTC)is a rare neuroendocrine tumor that originates from the parafollicular C cells of thyroid gland.Understanding the fundamental pathophysiology of MTC is essential for clinical manage-ment.Single-cell RNA sequencing(scRNA-seq)technology is a powerful tool for identifying distinct cell types,offering a new biological foundation for comprehending the MTC ecosystem and developing precise treatment.Methods Formalin fixed and paraffin-embedded(FFPE)samples of primary and adjacent non-cancerous tissues of three MTC cases were collected,and single-cell transcriptome data of MTC were obtained by using scRNA-seq technology.Annotated cell subpopulations were categorized and functionally enriched by principal component analysis,differential gene expression,and cell clustering analysis,to explore the biological process of tumor evolution that may be involved in each cell subpopulation.The copy number variation(CNV)profile was used to distinguish the malignancy of parafollicular thyroid cells,and the evolutionary trajectories of normal cells and tumor cells were revealed by the proposed time series analysis.The highly expressed genes in each cell subpopulation were analyzed by the FindAllMarker function of Seurat software,and verified by immunohistochemistry and fluorescence in situ hybridization.The prognostic value of specific cell subtypes was validated using large-scale public datasets.Results A total of 32,544 cells were obtained from the MTC tissue samples and 11,751 cells from the adjacent non-cancerous samples,which were classified into 7 heterogenous subpopulations by using R package of Seurat mod-ule.Copy number variations(CNVs)were significantly higher in tumor tissues than in adjacent non-tumor samples,predominantly enriched in subtypes C2 and C4.In addition,the pseudo-time for trajectory analysis suggested that the evolution of MTC tumor cells might begin with the C2 subtype,then transition to the early cancer sub-group C3,and further differentiate into four major malignant cell subpopulations C0,C1,C5 and C6.Survival analysis of a thyroid cancer cohort using the TCGA dataset revealed that high expression of genes linked to the C0 subcluster was correlated with poorer overall survival compared to low expression.Immunohistochemical staining showed that MAP3K4 was highly expressed in MTC tissues compared to adjacent non-cancerous tissues.Fluorescence in situ hybridization also confirmed the amplification of these two genes in MTC samples.Conclusions By conducting scRNA-seq on FFPE samples,we mapped the single-cell transcriptome of MTC,uncov-ering the tumor heterogeneity and unique biological features of each cellular subpopulation.The biological roles of identified tumor cell subpopulations such as C0 and C3 subtypes of parafollicular cells suggested the potential to discover new therapeutic targets and biomarkers for MTC,providing valuable insights for future translational and clinical research.
基金supported by grants from the Major Special Project of Fujian Province(2021NZ029009)the Natural Science foundation of Fujian Province(2019J01665).
文摘JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a nearly complete genome assembly of JUJUNCAO and reveal that JUJUNCAO is an allopolyploid that originated2.7 million years ago(mya).Its genome consists of two subgenomes,and subgenome A shares high collinear synteny with pearl millet.We also investigated the genome evolution of JUJUNCAO and suggest that the ancestral karyotype of Cenchrus split into the A and B ancestral karyotypes of JUJUNCAO.Comparative transcriptome and DNA methylome analyses revealed functional divergence of homeologous gene pairs between the two subgenomes,which was a further indication of asymmetric DNA methylation.The three types of centromeric repeat in the JUJUNCAO genome(CEN137,CEN148,and CEN156)may have evolved independently within each subgenome,with some introgressions of CEN156 from the B to the A subgenome.We investigated the photosynthetic characteristics of JUJUNCAO,revealing its typical C4 Kranz anatomy and high photosynthetic efficiency.NADP-ME and PEPCK appear to cooperate in the major C4 decarboxylation reaction of JUJUNCAO,which is different from other C4 photosynthetic subtypes and may contribute to its high photosynthetic efficiency and biomass yield.Taken together,our results provide insights into the highly efficient photosynthetic mechanism of JUJUNCAO and provide a valuable reference genome for future genetic and evolutionary studies,as well as genetic improvement of Cenchrus grasses.
