scholarly journals A comprehensive analysis of single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer

2018 ◽  
Author(s):  
Peng Zhang ◽  
Mingran Yang ◽  
Yiding Zhang ◽  
Shuai Xiao ◽  
Xinxing Lai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Single Cell ◽  
Early Stage ◽  
Cell Subset ◽  
Premalignant Lesions ◽  
Data Resource ◽  
Precise Diagnosis ◽  
Malignant Lesions ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

SummaryIntestinal-type gastric cancer is preceded by premalignant lesions including chronic atrophic gastritis (CAG) and intestinal metaplasia (IM), which are characterized as changes in cell types. In this study, for the first time, we systematically constructed a single-cell atlas for a total of 31,164 high-quality cells from gastric mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing (scRNA-seq). Based on the atlas, we construct a network underlying the changes of cellular and molecular characteristics of gastric epithelial cells across different lesions. We found the conversion of gland mucous cells (GMCs) toward a more intestinal-like stem cell phenotype during metaplasia, and identified OR51E1 as a novel marker for early-malignant enteroendocrine cells. We also found that HES6 might mark a goblet cell subset that precede morphologically identifiable goblet cells in IM mucosa, potentially aiding the identification of metaplasia at the early stage. Finally, we identified a panel of EGC-related specific signature, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions and provides an important data resource that will facilitate studies in gastritis-induced tumourigenesis and gastric cell biology.Significance StatementUnderstanding cellular characteristics in gastric premalignant and malignant lesions would help us better understand the gastric cancer (GC) pathogenesis. In this paper, for the first time, we systematically constructed a single-cell transcriptome network of human premalignant gastric mucosa and early GC (EGC) and derived novel findings from it. We identified OR51E1 as a novel marker for early-malignant enteroendocrine cells and a panel of genes as the EGC-specific signature, with clinical implications for the precise diagnosis of EGC. We also found HES6 might mark a goblet cell subset that precede morphologically identifiable goblet cells in IM mucosa, potentially aiding the identification of metaplasia at the early stage. Our study provided an unprecedented data resource that will facilitate studies underlying gastritis-induced tumorigenesis.

scholarly journals Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

Cell Reports ◽  
2019 ◽  
Vol 27 (6) ◽  
pp. 1934-1947.e5 ◽  
Author(s):  
Peng Zhang ◽  
Mingran Yang ◽  
Yiding Zhang ◽  
Shuai Xiao ◽  
Xinxing Lai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Single Cell ◽  
Premalignant Lesions ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

Cell Reports ◽  
2020 ◽  
Vol 30 (12) ◽  
pp. 4317 ◽  
Author(s):  
Peng Zhang ◽  
Mingran Yang ◽  
Yiding Zhang ◽  
Shuai Xiao ◽  
Xinxing Lai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Single Cell ◽  
Premalignant Lesions ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Single-cell transcriptome reveals the redifferentiation trajectories of the early stage of de novo shoot regeneration in Arabidopsis thaliana

2022 ◽  
Author(s):  
Guangyu Liu ◽  
Jie Li ◽  
Jiming Li ◽  
Zhiyong Chen ◽  
Peisi Yuan ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Shoot Regeneration ◽  
De Novo ◽  
Developmental Process ◽  
Early Stage ◽  
Cell Populations ◽  
Cell Heterogeneity ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

De novo shoot regeneration from a callus plays a crucial role in both plant biotechnology and the fundamental research of plant cell totipotency. Recent studies have revealed many regulatory factors involved in this developmental process. However. our knowledge of the cell heterogeneity and cell fate transition during de novo shoot regeneration is still limited. Here, we performed time-series single-cell transcriptome experiments to reveal the cell heterogeneity and redifferentiation trajectories during the early stage of de novo shoot regeneration. Based on the single-cell transcriptome data of 35,669 cells at five-time points, we successfully determined seven major cell populations in this developmental process and reconstructed the redifferentiation trajectories. We found that all cell populations resembled root identities and undergone gradual cell-fate transitions. In detail, the totipotent callus cells differentiated into pluripotent QC-like cells and then gradually developed into less differentiated cells that have multiple root-like cell identities, such as pericycle-like cells. According to the reconstructed redifferentiation trajectories, we discovered that the canonical regeneration-related genes were dynamically expressed at certain stages of the redifferentiation process. Moreover, we also explored potential transcription factors and regulatory networks that might be involved in this process. The transcription factors detected at the initial stage, QC-like cells, and the end stage provided a valuable resource for future functional verifications. Overall, this dataset offers a unique glimpse into the early stages of de novo shoot regeneration, providing a foundation for a comprehensive analysis of the mechanism of de novo shoot regeneration.

scholarly journals Critical roles of ICOS in controlling Foxp3-expressing T follicular cell subsets during early-stage germinal center reactions

2021 ◽  
Author(s):  
Vincent Panneton ◽  
Barbara C Mindt ◽  
Yasser Bouklouch ◽  
Jinsam Chang ◽  
Mariko Witalis ◽  
...  
Keyword(s):  
B Cells ◽  
Single Cell ◽  
Transcriptome Analysis ◽  
Germinal Center ◽  
Early Stage ◽  
Dependent Manner ◽  
Flow Cytometry Data ◽  
Costimulatory Receptor ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

The inducible costimulator (ICOS) is a T cell costimulatory receptor critical for humoral immunity. In mice and humans, ICOS deficiency leads to a lack of T follicular helper (Tfh) cells and protective antibodies. However, the role of ICOS in T follicular regulatory (Tfr) cell generation and function remains poorly understood. Using Foxp3-cre-mediated ICOS knockout (ICOS FC) mice, we show that T regulatory (Treg)-specific ICOS deletion drastically reduces the number of Tfr cells without altering Treg cell numbers. Further, we observed a lowered ratio of antigen-specific germinal center B (GC B) cells and increased anti-nuclear antibodies in ICOS FC mice, suggesting a rise of autoreactive GC B cells. Single-cell transcriptome analysis revealed shifts in transitory Tfr precursor populations in immunized ICOS FC mice. Mechanistically, our data suggest that ICOS promotes the Treg-to-Tfr transition by regulating KLF2 and NFAT2 with downstream impacts on Bcl6 and CXCR5 expression. Importantly, we discovered a Tfr subset originating from Foxp3- precursors by analyzing flow cytometry data of immunized mice in which ICOS expression in Foxp3+ cells was ablated at different stages of GC reactions. Consistently, single-cell transcriptome analysis of global follicular T cells revealed a subset of Tfh-like cells beginning to express Foxp3 at day 6 post-immunization. These Tfh-like Tfr cells appear to promote GC B cell expansion and plasma cell differentiation in an ICOS-dependent manner. Taken together, we propose that Tfr cells derived from natural Tregs suppress the expansion of autoreactive GC B cells whereas Tfh-like Tfr cells promote early-stage GC output. Further, these Tfr subsets depend on ICOS costimulation for their differentiation or function.

scholarly journals Single-cell transcriptome analyses recapitulate the cellular and developmental responses to abiotic stresses in rice

2020 ◽  
Author(s):  
Yu Wang ◽  
Qing Huan ◽  
Xiao Chu ◽  
Ke Li ◽  
Wenfeng Qian
Keyword(s):  
Single Cell ◽  
Abiotic Stresses ◽  
Developmental Trajectories ◽  
Cell Types ◽  
Data Resource ◽  
A Cell ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Developmental Responses ◽  
Computational Analyses

ABSTRACTThe metabolism and reproduction of plants depend on the division of labors among cells. However, cells with various functions are often studied as a bulk where their specificities were diluted. Here, we apply single-cell RNA sequencing to the aerial part of rice seedlings growing in various environments. We capture the transcriptomes of thousands of cells, identify all major cell types, and reconstruct their developmental trajectories. We find that abiotic stresses not only affect gene expression in a cell-type-specific manner but also have impacts on the physical size of cells and the composition of cell populations. We validate some of these conclusions with microscopy and provide developmental mechanisms with computational analyses. Collectively, our study represents a benchmark-setting data resource of single-cell transcriptome atlas in rice and an illustration of exploiting such resource to drive discoveries in plant biology.

scholarly journals Single cell transcriptome atlas of mouse mammary epithelial cells across development

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Bhupinder Pal ◽  
Yunshun Chen ◽  
Michael J. G. Milevskiy ◽  
François Vaillant ◽  
Lexie Prokopuk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Developmental Stages ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Single Cells ◽  
Chromatin Accessibility ◽  
Mammary Epithelial ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.

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