Cellular heterogeneity and immune microenvironment revealed by single-cell transcriptome in venous malformation and cavernous venous malformation

2022 ◽  
Vol 162 ◽  
pp. 130-143
Author(s):  
Yongyun Li ◽  
Jie Yang ◽  
Yazhuo Huang ◽  
Shengfang Ge ◽  
Xin Song ◽  
...  
Keyword(s):  
Single Cell ◽  
Venous Malformation ◽  
Cellular Heterogeneity ◽  
Immune Microenvironment ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses

2021 ◽  
Author(s):  
Rong Lu ◽  
HUMBERTO CONTRERAS-TRUJILLO ◽  
JIYA EERDENG ◽  
SAMIR AKRE ◽  
DU JIANG ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Dna Barcode ◽  
Treatment Resistance ◽  
Intratumoral Heterogeneity ◽  
Integrated System ◽  
Cellular Heterogeneity ◽  
Gene Expression Signatures ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression signatures respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover an unexpected yet common form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression signatures. Our integrated system directly and effectively interrogates the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.

scholarly journals Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Humberto Contreras-Trujillo ◽  
Jiya Eerdeng ◽  
Samir Akre ◽  
Du Jiang ◽  
Jorge Contreras ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Dna Barcode ◽  
Treatment Resistance ◽  
Experimental System ◽  
Transcriptome Profiling ◽  
Intratumoral Heterogeneity ◽  
Cellular Heterogeneity ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractCellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.

scholarly journals Combinatorial action of transcription factors in open chromatin contributes to early cellular heterogeneity and organizer mesendoderm specification

2020 ◽  
Author(s):  
Ann Rose Bright ◽  
Siebe van Genesen ◽  
Qingqing Li ◽  
Simon J. van Heeringen ◽  
Alexia Grasso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Single Cell ◽  
Marginal Zone ◽  
Chromatin Accessibility ◽  
Cellular Heterogeneity ◽  
Open Chromatin ◽  
Cell Clusters ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

ABSTRACTDuring gastrulation, mesoderm is induced in pluripotent cells, concomitant with dorsal-ventral patterning and establishing of the dorsal axis. How transcription factors operate within the constraints of chromatin accessibility to mediate these processes is not well-understood. We applied chromatin accessibility and single cell transcriptome analyses to explore the emergence of heterogeneity and underlying gene-regulatory mechanisms during early gastrulation in Xenopus. ATAC-sequencing of pluripotent animal cap cells revealed a state of open chromatin of transcriptionally inactive lineage-restricted genes, whereas chromatin accessibility in dorsal marginal zone cells more closely reflected the transcriptional activity of genes. We characterized single cell trajectories in animal cap and dorsal marginal zone in early gastrula embryos, and inferred the activity of transcription factors in single cell clusters by integrating chromatin accessibility and single cell RNA-sequencing. We tested the activity of organizer-expressed transcription factors in mesoderm-competent animal cap cells and found combinatorial effects of these factors on organizer gene expression. In particular the combination of Foxb1 and Eomes induced a gene expression profile that mimicked those observed in head and trunk organizer single cell clusters. In addition, genes induced by Eomes, Otx2 or the Irx3-Otx2 combination, were enriched for promoters with maternally regulated H3K4me3 modifications, whereas promoters selectively induced by Lhx8 were marked more frequently by zygotically controlled H3K4me3. Our results show that combinatorial activity of zygotically expressed transcription factors acts on maternally-regulated accessible chromatin to induce organizer gene expression.

scholarly journals Single Cell Transcriptome Helps Better Understanding Crosstalk in Diabetic Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Chunyang Du ◽  
Yunzhuo Ren ◽  
Guixin Li ◽  
Yan Yang ◽  
Zhe Yan ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Single Cell ◽  
Diabetic Kidney Disease ◽  
Cellular Heterogeneity ◽  
Specific Level ◽  
Glomerular Cell ◽  
Diabetic Kidney ◽  
Cellular Targets ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Years of research revealed that crosstalk extensively existed among kidney cells, cell factors and metabolites and played an important role in the development of diabetic kidney disease (DKD). In the last few years, single-cell RNA sequencing (scRNA-seq) technology provided new insight into cellular heterogeneity and genetic susceptibility regarding DKD at cell-specific level. The studies based on scRNA-seq enable a much deeper understanding of cell-specific processes such as interaction between cells. In this paper, we aim to review recent progress in single cell transcriptomic analyses of DKD, particularly highlighting on intra- or extra-glomerular cell crosstalk, cellular targets and potential therapeutic strategies for DKD.

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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