scholarly journals Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging

2020 ◽  
Author(s):  
Xinying Guo ◽  
Bangyan Zhang ◽  
Fernando Gomez-Pinilla ◽  
Fan Gao ◽  
Zhen Zhao
Keyword(s):  
Traumatic Brain Injury ◽  
Endothelial Cells ◽  
Brain Injury ◽  
Single Cell ◽  
Transcriptomic Analysis ◽  
Pathological Feature ◽  
Molecular Signatures ◽  
Cerebrovascular Injury ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractCerebrovascular injury is a common pathological feature of a spectrum of neurological disorders including traumatic brain injury (TBI), stroke, Alzheimer’s disease (AD), as well as aging. Vascular manifestations among these conditions are similar indeed, including the breakdown of the blood-brain barrier (BBB). However, whether there is a common molecular mechanism underlying the vascular changes among these conditions remains elusive. Here, we report secondary transcriptomic analysis on cerebrovascular cells based single-cell RNA-seq datasets of mouse models of mild TBI and aging, with a focus on endothelial cells and pericytes. We identify several molecular signatures commonly found between mTBI and aging vasculature, including Adamts1, Rpl23a, Tmem252, Car4, Serpine2, and Ndnf in endothelial cells, and Rps29 and Sepp1 in pericytes. These markers may represent the shared endophenotype of microvascular injury and be considered as cerebrovascular injury responsive genes. Additionally, pathway analysis on differentially expressed genes demonstrated alterations in common pathways between mTBI and aging, including vascular development and extracellular matrix pathways in endothelial cells. Hence, our analysis suggests that cerebrovascular injury triggered by different neurological conditions may share common molecular signatures, which may only be detected at the single-cell transcriptome level.

Abstract 103: Single Cell Transcriptome Analyses Reveal Novel Targets for Therapeutic Neovascularisation by Resident Endothelial Cells in the Heart

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Ziwen Li ◽  
Emmanouil G Solomonidis ◽  
Rodger Duffin ◽  
Ross Dobie ◽  
Marlene S Mahalhaes ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Novel Targets ◽  
Transcriptome Analyses ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals Single-cell transcriptome analysis of embryonic and adult endothelial cells allows to rank the hemogenic potential of post-natal endothelium

2021 ◽  
Author(s):  
Artem Adamov ◽  
Yasmin Natalia Serina Sechanecia ◽  
Christophe Lancrin
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Hematopoietic Stem Cells ◽  
Single Cell ◽  
Rational Design ◽  
Continuous Production ◽  
Cellular Reprogramming ◽  
Hematopoietic Stem ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Hematopoietic stem cells are crucial for the continuous production of blood cells during life. The transplantation of these cells is one of the most common treatments to cure patient suffering of blood diseases. However, the lack of suitable donors is a major limitation. One option to get hematopoietic stem cells matching perfectly a patient is cellular reprogramming. Hematopoietic stem cells emerge from endothelial cells in blood vessels during embryogenesis through the endothelial to hematopoietic transition. Here, we used single-cell transcriptomics analysis to compare embryonic and post-natal endothelial cells to investigate the potential of adult vasculature to be reprogrammed in hematopoietic stem cells. Although transcriptional similarities have been found between embryonic and adult endothelial cells, we found some key differences in term of transcription factors expression. There is a deficit of expression of Runx1, Tal1, Lyl1 and Cbfb in adult endothelial cells compared to their embryonic counterparts. Using a combination of gene expression profiling and gene regulatory network analysis, we found that endothelial cells from the pancreas, brain, kidney and liver appear to be the most suitable targets for cellular reprogramming into hematopoietic stem cells. Overall, our work provides an important resource for the rational design of a reprogramming strategy for the generation of hematopoietic stem cells.

scholarly journals Mapping morphological malformation to genetic dysfunction in blood vessel organoids with 22q11.2 Deletion Syndrome

2021 ◽  
Author(s):  
Siyu He ◽  
Cong Xu ◽  
Yeh-Hsing Lao ◽  
Shradha Chauhan ◽  
Yang Xiao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessel ◽  
Single Cell ◽  
22Q11.2 Deletion Syndrome ◽  
Vascular Network ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Mural Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

DiGeorge Syndrome, or 22q11.2 deletion syndrome (22q11.2 DS), is a genetic disorder caused by microdeletions in chromosome 22, impairing the function of endothelial cells (EC) and/or mural cells and leading to deficits in blood vessel development such as abnormal aortic arch morphology, tortuous retinal vessels, and tetralogy of Fallot. The mechanism by which dysfunctional endothelial cells and pericytes contribute to the vasculopathy, however, remains unknown. In this study, we used human blood vessel organoids (VOs) generated from iPSC of 22q11.2 DS patients to model the vascular malformations and genetic dysfunctions. We combined high-resolution lightsheet imaging and single-cell transcriptome analysis to link the genetic profile and vascular phenotype at the single-cell level. We developed a comprehensive analytical methodology by integrating deep learning-mediated blood vessel segmentation, network graph construction, and tessellation analysis for automated morphology characterization. We report that 22q11.2DS VOs demonstrate a smaller size with increased angiogenesis/sprouting, suggesting a less stable vascular network. Overall, clinical presentations of smaller vascular diameter, less connected vasculature, and increased branch points were recapitulated in 22q11.2DS VOs. Single-cell transcriptome profiling showed heterogeneity in both 22q11.2DS and control VOs, but the former demonstrated alterations in endothelial characteristics that are organ-specific and suggest a perturbation in the vascular developmental process. Intercellular communication analysis indicated that the vascular dysfunctions in 22q11.2 deletion were due to a lower cell-cell contact and upregulated extracellular matrix organization involving collagen and fibronectin. Voronoi diagram-based tessellation analysis also indicated that the colocalization of endothelial tubes and mural cells was different between control and 22q11.2 VOs, indicating that alterations in EC and mural interactions might contribute to the deficits in vascular network formation. This study illustrates the utility of VO in revealing the pathogenesis of 22q11.2DS vasculopathy.

scholarly journals Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

2021 ◽  
Vol 15 ◽  
Author(s):  
Bing Chen ◽  
Matthew C. Banton ◽  
Lolita Singh ◽  
David B. Parkinson ◽  
Xin-peng Dun
Keyword(s):  
Endothelial Cells ◽  
Data Analysis ◽  
Single Cell ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Cell Types ◽  
Transcriptome Data ◽  
Single Cell Rna Sequencing ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

The advances in single-cell RNA sequencing technologies and the development of bioinformatics pipelines enable us to more accurately define the heterogeneity of cell types in a selected tissue. In this report, we re-analyzed recently published single-cell RNA sequencing data sets and provide a rationale to redefine the heterogeneity of cells in both intact and injured mouse peripheral nerves. Our analysis showed that, in both intact and injured peripheral nerves, cells could be functionally classified into four categories: Schwann cells, nerve fibroblasts, immune cells, and cells associated with blood vessels. Nerve fibroblasts could be sub-clustered into epineurial, perineurial, and endoneurial fibroblasts. Identified immune cell clusters include macrophages, mast cells, natural killer cells, T and B lymphocytes as well as an unreported cluster of neutrophils. Cells associated with blood vessels include endothelial cells, vascular smooth muscle cells, and pericytes. We show that endothelial cells in the intact mouse sciatic nerve have three sub-types: epineurial, endoneurial, and lymphatic endothelial cells. Analysis of cell type-specific gene changes revealed that Schwann cells and endoneurial fibroblasts are the two most important cell types promoting peripheral nerve regeneration. Analysis of communication between these cells identified potential signals for early blood vessel regeneration, neutrophil recruitment of macrophages, and macrophages activating Schwann cells. Through this analysis, we also report appropriate marker genes for future single cell transcriptome data analysis to identify cell types in intact and injured peripheral nerves. The findings from our analysis could facilitate a better understanding of cell biology of peripheral nerves in homeostasis, regeneration, and disease.

scholarly journals Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development

2018 ◽  
Author(s):  
Morgan Oatley ◽  
Özge Vargel Bölükbasi ◽  
Valentine Svensson ◽  
Maya Shvartsman ◽  
Kerstin Ganter ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Tca Cycle ◽  
Notch Signalling ◽  
Haematopoietic Stem Cells ◽  
Expression Of Genes ◽  
The Tca Cycle ◽  
Stem And Progenitor Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractThe endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development.

scholarly journals Single-Cell Transcriptome Atlas of Murine Endothelial Cells

Cell ◽  
2020 ◽  
Vol 180 (4) ◽  
pp. 764-779.e20 ◽  
Author(s):  
Joanna Kalucka ◽  
Laura P.M.H. de Rooij ◽  
Jermaine Goveia ◽  
Katerina Rohlenova ◽  
Sébastien J. Dumas ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

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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