scholarly journals Surveying Brain Tumor Heterogeneity by Single-Cell RNA Sequencing of Multi-sector Biopsies

2020 ◽  
Author(s):  
Kai Yu ◽  
Yuqiong Hu ◽  
Fan Wu ◽  
Qiufang Guo ◽  
Zenghui Qian ◽  
...  
Keyword(s):  
Single Cell ◽  
Expression Profiles ◽  
Chinese Patients ◽  
Rna Seq ◽  
Receptor Interactions ◽  
Cell Components ◽  
Dynamic Cell ◽  
Spatial Level ◽  
Cell Expression ◽  
Level Analysis

ABSTRACTBrain tumors are among the most challenging human tumors for which the mechanisms driving progression and heterogeneity remain poorly understood. We combined single-cell RNA-seq with multisector biopsies to sample and analyze single-cell expression profiles of gliomas from 13 Chinese patients. After classifying individual cells, we generated a spatial and temporal landscape of glioma that revealed the patterns of invasion between the different sub-regions of gliomas. We also used single-cell inferred CNVs and pseudotime trajectories to inform on the crucial branches that dominate tumor progression. The dynamic cell components of the multi-region biopsy analysis allowed us to spatially deconvolute with unprecedented accuracy the transcriptomic features of the core and those of the periphery of glioma at single cell level. Through this rich and geographically detailed dataset, we were also able to characterize and construct the chemokine and chemokine receptor interactions that exist among different tumor and non-tumor cells. This study provides the first spatial-level analysis of the cellular states that characterize human gliomas. It also presents an initial molecular map of the crosstalks between glioma cells and the surrounding microenvironment with single cell resolution.

scholarly journals Surveying brain tumor heterogeneity by single-cell RNA-sequencing of multi-sector biopsies

2020 ◽  
Vol 7 (8) ◽  
pp. 1306-1318 ◽  
Author(s):  
Kai Yu ◽  
Yuqiong Hu ◽  
Fan Wu ◽  
Qiufang Guo ◽  
Zenghui Qian ◽  
...  
Keyword(s):  
Single Cell ◽  
Expression Profiles ◽  
Copy Number Variations ◽  
Chinese Patients ◽  
Rna Seq ◽  
Receptor Interactions ◽  
Cell Components ◽  
Dynamic Cell ◽  
Spatial Level ◽  
Cell Expression

Abstract Brain tumors are among the most challenging human tumors for which the mechanisms driving progression and heterogeneity remain poorly understood. We combined single-cell RNA-seq with multi-sector biopsies to sample and analyze single-cell expression profiles of gliomas from 13 Chinese patients. After classifying individual cells, we generated a spatial and temporal landscape of glioma that revealed the patterns of invasion between the different sub-regions of gliomas. We also used single-cell inferred copy number variations and pseudotime trajectories to inform on the crucial branches that dominate tumor progression. The dynamic cell components of the multi-region biopsy analysis allowed us to spatially deconvolute with unprecedented accuracy the transcriptomic features of the core and those of the periphery of glioma at single-cell level. Through this rich and geographically detailed dataset, we were also able to characterize and construct the chemokine and chemokine receptor interactions that exist among different tumor and non-tumor cells. This study provides the first spatial-level analysis of the cellular states that characterize human gliomas. It also presents an initial molecular map of the cross-talks between glioma cells and the surrounding microenvironment with single-cell resolution.

scholarly journals Single-Cell Expression Landscape of SARS-CoV-2 Receptor ACE2 and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1250
Author(s):  
Guangchun Han ◽  
Ansam Sinjab ◽  
Kieko Hara ◽  
Warapen Treekitkarnmongkol ◽  
Patrick Brennan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Cell ◽  
Cancer Patients ◽  
Expression Profiles ◽  
Lung Cells ◽  
Alveolar Type ◽  
Specific Expression ◽  
Lung Cancer Patients ◽  
Normal Tissues ◽  
Cell Expression

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of ACE2 and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of ACE2 and SARS-CoV-2-priming proteases TMPRSS2 and TMPRSS4 in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of ACE2, TMPRSS2, and TMPRSS4. Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that ACE2 levels were highest in normal alveolar type 2 (AT2) cells and that TMPRSS2 was expressed in 65% of normal AT2 cells. Conversely, the expression of TMPRSS4 was highest and most frequently detected (75%) in lung cells with malignant features. ACE2-positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated HHIP, and the scavengers CD36 and DMBT1. Notably, the viral scavenger DMBT1 was significantly positively correlated with ACE2 expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.

The characteristics of mesenteric adipose tissue attached to different intestinal segments and their roles in immune regulation

2022 ◽  
Author(s):  
Haowei Zhang ◽  
Yujin Ding ◽  
Qin Zeng ◽  
Dandan Wang ◽  
Ganglei Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Immune Regulation ◽  
Expression Profiles ◽  
Critical Role ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Mesenteric Adipose Tissue ◽  
Cell Components ◽  
Subsequent Effect

Background: Mesenteric adipose tissue (MAT) plays a critical role in the intestinal physiological ecosystems. Small and large intestines have evidently intrinsic and distinct characteristics. However, whether there exist any mesenteric differences adjacent to the small and large intestines (SMAT and LMAT) has not been properly characterized. We studied the important facets of these differences, such as morphology, gene expression, cell components and immune regulation of MATs, to characterize the mesenteric differences. Methods: The SMAT and LMAT of mice were utilized for comparison of tissue morphology. Paired mesenteric samples were analyzed by RNA-seq to clarify gene expression profiles. MAT partial excision models were constructed to illustrate the immune regulation roles of MATs, and 16S-seq was applied to detect the subsequent effect on microbiota. Results: Our data show that different segments of mesenteries have different morphological structures. SMAT not only has smaller adipocytes but also contains more fat-associated lymphoid clusters than LMAT. The gene expression profile is also discrepant between these two MATs in mice. B-cell markers were abundantly expressed in SMAT, while development-related genes were highly expressed in LMAT. Adipose-derived stem cells of LMAT exhibited higher adipogenic potential and lower proliferation rates than those of SMAT. In addition, SMAT and LMAT play different roles in immune regulation and subsequently affect microbiota components. Finally, our data clarified the described differences between SMAT and LMAT in humans. Conclusions: There were significant differences in cell morphology, gene expression profiles, cell components, biological characteristics, and immune and microbiota regulation roles between regional MATs.

Single-cell expression profiles of melanoma

Science ◽  
2016 ◽  
Vol 352 (6282) ◽  
pp. 183-185
Author(s):  
L. M. Zahn
Keyword(s):  
Single Cell ◽  
Expression Profiles ◽  
Cell Expression

scholarly journals A map of tumor–host interactions in glioma at single-cell resolution

GigaScience ◽  
2020 ◽  
Vol 9 (10) ◽  
Author(s):  
Francesca Pia Caruso ◽  
Luciano Garofano ◽  
Fulvio D'Angelo ◽  
Kai Yu ◽  
Fuchou Tang ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Cross Talk ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Sequencing Data ◽  
Host Interaction ◽  
Receptor Interactions ◽  
Single Cell Rna Sequencing

ABSTRACT Background Single-cell RNA sequencing is the reference technique for characterizing the heterogeneity of the tumor microenvironment. The composition of the various cell types making up the microenvironment can significantly affect the way in which the immune system activates cancer rejection mechanisms. Understanding the cross-talk signals between immune cells and cancer cells is of fundamental importance for the identification of immuno-oncology therapeutic targets. Results We present a novel method, single-cell Tumor–Host Interaction tool (scTHI), to identify significantly activated ligand–receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand–receptor interactions in glioma using 6 publicly available human glioma datasets encompassing 57,060 gene expression profiles from 71 patients. By leveraging this large-scale collection we show that unexpected cross-talk partners are highly conserved across different datasets in the majority of the tumor samples. This suggests that shared cross-talk mechanisms exist in glioma. Conclusions Our results provide a complete map of the active tumor–host interaction pairs in glioma that can be therapeutically exploited to reduce the immunosuppressive action of the microenvironment in brain tumor.

scholarly journals Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines

2020 ◽  
Vol 123 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Luciane T. Kagohara ◽  
Fernando Zamuner ◽  
Emily F. Davis-Marcisak ◽  
Gaurav Sharma ◽  
Michael Considine ◽  
...  
Keyword(s):  
Single Cell ◽  
Tyrosine Kinases ◽  
Expression Profiles ◽  
Tumour Cells ◽  
Response To Treatment ◽  
Global Changes ◽  
Rna Seq ◽  
Mechanisms Of Resistance ◽  
Mesenchymal Transition ◽  
Days Of Therapy

Abstract Background Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical to delay acquired resistance. Methods We generated the first comprehensive multi-omics, bulk and single-cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases by TFAP2A transcription factor, and epithelial-to-mesenchymal transition (EMT). Results Single-cell RNA-seq demonstrates heterogeneity, with cell-specific TFAP2A and VIM expression profiles in response to treatment and also with global changes to various signalling pathways. RNA-seq and ATAC-seq reveal global changes within 5 days of therapy, suggesting early onset of mechanisms of resistance; and corroborates cell line heterogeneity, with different TFAP2A targets or EMT markers affected by therapy. Lack of TFAP2A expression is associated with HNSCC decreased growth, with cetuximab and JQ1 increasing the inhibitory effect. Regarding the EMT process, short-term cetuximab therapy has the strongest effect on inhibiting migration. TFAP2A silencing does not affect cell migration, supporting an independent role for both mechanisms in resistance. Conclusion Overall, we show that immediate adaptive transcriptional and epigenetic changes induced by cetuximab are heterogeneous and cell type dependent; and independent mechanisms of resistance arise while tumour cells are still sensitive to therapy.

scholarly journals A Preliminary Single-Cell RNA-Seq Analysis of Embryonic Cells That Express Brachyury in the Amphioxus, Branchiostoma japonicum

2021 ◽  
Vol 9 ◽  
Author(s):  
Noriyuki Satoh ◽  
Hitoshi Tominaga ◽  
Masato Kiyomoto ◽  
Kanako Hisata ◽  
Jun Inoue ◽  
...  
Keyword(s):  
Single Cell ◽  
Hox Genes ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Embryonic Cells ◽  
Rna Seq ◽  
Tail Bud ◽  
Developmental Features ◽  
Number Of Cells ◽  
In Cells

Among chordate taxa, the cephalochordates diverged earlier than urochordates and vertebrates; thus, they retain unique, primitive developmental features. In particular, the amphioxus notochord has muscle-like properties, a feature not seen in urochordates or vertebrates. Amphioxus contains two Brachyury genes, Bra1 and Bra2. Bra2 is reportedly expressed in the blastopore, notochord, somites, and tail bud, in contrast to a low level of Bra1 expression only in notochord. To distinguish the expression profiles of the two Brachyury genes at the single-cell level, we carried out single-cell RNA-seq (scRNA-seq) analysis using the amphioxus, Branchiostoma japonicum. This scRNA-seq analysis classified B. japonicum embryonic cells into 15 clusters at developmental stages from midgastrula to early swimming larva. Brachyury was expressed in cells of clusters 4, 5, 8, and 9. We first confirmed that cluster 8 comprises cells that form somites since this cluster specifically expresses four myogenic factor genes. Cluster 9 contains a larger number of cells with high levels of Bra2 expression and a smaller number of cells with Bra1 expression. Simultaneous expression in cluster 9 of tool-kit genes, including FoxA, Goosecoid, and hedgehog, showed that this cluster comprises cells that form the notochord. Expression of Bra2, but not Bra1, in cells of clusters 4 and 5 at the gastrula stage together with expression of Wnt1 and Caudal indicates that clusters 4 and 5 comprise cells of the blastopore, which contiguously form the tail bud. In addition, Hox1, Hox3, and Hox4 were highly expressed in Bra2-expressing clusters 4, 5, 8, and 9 in a temporally coordinated manner, suggesting roles of anterior Hox genes in specification of mesodermal organs, including somites, notochord, and tail bud. This scRNA-seq analysis therefore highlights differences between the two Brachyury genes in relation to embryonic regions in which they are expressed and their levels of expression. Bra2 is the ancestral Brachyury in amphioxus, since expression in the blastopore is shared with other deuterostomes. On the other hand, Bra1 is a duplicate copy and likely evolved a supplementary function in notochord and somite formation in the Branchiostoma lineage.

scholarly journals Bulk Tissue Cell Type Deconvolution with Multi-Subject Single-Cell Expression Reference

2018 ◽  
Author(s):  
Xuran Wang ◽  
Jihwan Park ◽  
Katalin Susztak ◽  
Nancy R. Zhang ◽  
Mingyao Li
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Tissue Cell ◽  
Specific Gene ◽  
Rna Seq ◽  
Cell Type ◽  
Cell Type Specific ◽  
Cell Expression

AbstractWe present MuSiC, a method that utilizes cell-type specific gene expression from single-cell RNA sequencing (RNA-seq) data to characterize cell type compositions from bulk RNA-seq data in complex tissues. When applied to pancreatic islet and whole kidney expression data in human, mouse, and rats, MuSiC outperformed existing methods, especially for tissues with closely related cell types. MuSiC enables characterization of cellular heterogeneity of complex tissues for identification of disease mechanisms.

scholarly journals Integrated single cell and bulk multi-omics reveals heterogeneity and early changes in pathways associated with cetuximab resistance in HNSCC sensitive cell lines

2019 ◽  
Author(s):  
Luciane Tsukamoto Kagohara ◽  
Fernando Zamuner ◽  
Michael Considine ◽  
Jawara Allen ◽  
Srinivasan Yegnasubramanian ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Cells ◽  
Tyrosine Kinases ◽  
Expression Profiles ◽  
Response To Treatment ◽  
Global Changes ◽  
Rna Seq ◽  
Mechanisms Of Resistance ◽  
Mesenchymal Transition ◽  
Cetuximab Therapy

Identifying potential mechanisms of resistance while tumor cells still respond to therapy is critical to delay acquired resistance. We generated the first comprehensive multi-omics, bulk and single cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases through the transcription factor TFAP2A, and epithelial-to-mesenchymal transition (EMT) process. Single cell RNA-seq demonstrates heterogeneity, with cell specific TFAP2A and VIM expression profiles in response to treatment. RNA-seq and ATAC-seq reveal global changes within five days of cetuximab therapy, suggesting early onset of mechanisms of resistance; and corroborates cell line heterogeneity, with different TFAP2A targets or EMT markers affected by therapy. Lack of TFAP2A reduces HNSCC growth and is enhanced by cetuximab and JQ1. Regarding the EMT process, short term cetuximab therapy has the strongest effect on inhibiting migration. TFAP2A silencing does not affect cell migration, supporting an independent role for both mechanisms in resistance. Overall, we show that immediate adaptive transcriptional and epigenetic changes induced by cetuximab are heterogeneous and cell type dependent; and independent mechanisms of resistance arise while tumor cells are still sensitive to therapy.

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