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.

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 A Web Portal and Workbench for Biological Dissection of Single Cell COVID-19 Host Responses

2021 ◽  
Author(s):  
Kang Jin ◽  
Eric E Bardes ◽  
Alexis Mitelpunkt ◽  
Yunguan Jake Wang ◽  
Surbhi Bhatnagar ◽  
...  
Keyword(s):  
Single Cell ◽  
Gene Signature ◽  
Host Responses ◽  
Web Portal ◽  
Tissue Samples ◽  
Cell Recruitment ◽  
Expression Of Genes ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Cell Activator

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a reusable datamine to allow users to compare and explore these data for insight, inference, and hypothesis generation. To accomplish this, we harmonized datasets from blood, bronchoalveolar lavage and tissue samples from COVID-19 and other control conditions and derived a compendium of gene signature modules per cell type, subtype, clinical condition and compartment. We demonstrate approaches for exploring and evaluating their significance via a new interactive web portal (ToppCell). As examples, we develop three hypotheses: (1) a multicellular signaling cascade among alternatively differentiated monocyte-derived macrophages whose tasks include T cell recruitment and activation; (2) novel platelet subtypes with drastically modulated expression of genes responsible for adhesion, coagulation and thrombosis; (3) a multilineage cell activator network able to drive extrafollicular B maturation via an ensemble of genes extensively associated with risk for developing autoimmunity.

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 reveals a new dynamical function of transcription factors during embryonic hematopoiesis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Isabelle Bergiers ◽  
Tallulah Andrews ◽  
Özge Vargel Bölükbaşı ◽  
Andreas Buness ◽  
Ewa Janosz ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Endothelial Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Cell Transcriptome ◽  
Dynamical Function ◽  
Single Cell Transcriptome

Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers. Within the heptad, we identified two sets of factors of opposing functions: one (Erg/Fli1) promoting the endothelial cell fate, the other (Runx1/Gata2) promoting the hematopoietic fate. Surprisingly, our data suggest that even though Fli1 initially supports the endothelial cell fate, it acquires a pro-hematopoietic role when co-expressed with Runx1. This work demonstrates the power of single-cell RNA-sequencing for characterizing complex transcription factor dynamics.

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.

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 Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons

2017 ◽  
Author(s):  
Ping Wang ◽  
Dejian Zhao ◽  
Herbert M. Lachman ◽  
Deyou Zheng
Keyword(s):  
Single Cell ◽  
Gene Networks ◽  
Developmental Stages ◽  
Cell Types ◽  
Autism Spectrum ◽  
Inhibitory Neurons ◽  
Expression Of Genes ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Upregulated Genes

AbstractAutism spectrum disorder (ASD) is highly heritable but genetically heterogeneous. The affected neural circuits and cell types remain unclear and may vary at different developmental stages. By analyzing multiple sets of human single cell transcriptome profiles, we found that ASD candidates showed enriched gene expression in neurons, especially in inhibitory neurons. ASD candidates were also more likely to be the hubs of the co-expressed module that is highly expressed in inhibitory neurons, a feature not detected for excitatory neurons. In addition, we found that upregulated genes in multiple ASD cortex samples were also enriched with genes highly expressed in inhibitory neurons, suggesting a potential increase of inhibitory neurons and an imbalance in the ratio between excitatory and inhibitory neurons. Furthermore, the downstream targets of several ASD candidates, such as CHD8, EHMT1 and SATB2, also displayed enriched expression in inhibitory neurons. Taken together, our analysis of single cell transcriptomic data suggest that inhibitory neurons may be the major neuron subtype affected by the disruption of ASD gene networks, providing single cell functional evidence to support the excitatory/inhibitory (E/I) imbalance hypothesis.

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