Single-Cell Transcriptomics Reveals Endothelial Plasticity During Diabetic Atherogenesis

Published on May 19, 2021in Frontiers in Cell and Developmental Biology5.201
· DOI :10.3389/FCELL.2021.689469
Guizhen Zhao3
Estimated H-index: 3
Haocheng Lu8
Estimated H-index: 8
+ 5 AuthorsJifeng Zhang36
Estimated H-index: 36
#1Lukas Tombor (Goethe University Frankfurt)H-Index: 5
#2David John (Goethe University Frankfurt)H-Index: 17
Last. Stefanie Dimmeler (Goethe University Frankfurt)H-Index: 165
view all 24 authors...
Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient cha...
4 CitationsSource
#1Aitor Andueza (Georgia Institute of Technology)H-Index: 1
#2Sandeep Kumar (Georgia Institute of Technology)H-Index: 1
Last. Hanjoong Jo (Georgia Institute of Technology)H-Index: 73
view all 8 authors...
Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNA-seq) and scATAC-seq study using endothelial-enriched single cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation (PCL) model. We find eight EC clusters along with immune cells, fibroblasts, and smooth muscle cells....
2 CitationsSource
#1Takashi Shimizu (UTokyo: University of Tokyo)H-Index: 1
#2Kazuaki Maruyama (UTokyo: University of Tokyo)H-Index: 3
Last. Youichiro Wada (UTokyo: University of Tokyo)H-Index: 28
view all 5 authors...
Protein kinase R-like endoplasmic reticulum kinase (PERK) is one of the endoplasmic reticulum (ER) stress sensors. PERK loss-of-function mutations are known to cause Wolcott-Rallison syndrome. This disease is characterized by early-onset diabetes mellitus, skeletal dysplasia, and cardiac valve malformation. To understand the role of PERK in valve formation in vivo, we used an endothelial-specific PERK conditional knockout mice as well as in vitro PERK inhibition assays. We used ProteoStat dyes t...
#1David T. Paik (Cardiovascular Institute of the South)H-Index: 14
#2Lei Tian (Cardiovascular Institute of the South)H-Index: 16
Last. Joseph C. Wu (Cardiovascular Institute of the South)H-Index: 122
view all 10 authors...
Background: Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. Whereas these functional differences are presumably i...
8 CitationsSource
#1Nan W. Hultgren (UCI: University of California, Irvine)H-Index: 3
#2Jennifer S. Fang (UCI: University of California, Irvine)H-Index: 15
Last. Christopher C.W. Hughes (UCI: University of California, Irvine)H-Index: 61
view all 13 authors...
Slug (SNAI2), a member of the well-conserved Snail family of transcription factors, has multiple developmental roles, including in epithelial-to-mesenchymal transition (EMT). Here, we show that Slug is critical for the pathological angiogenesis needed to sustain tumor growth, and transiently necessary for normal developmental angiogenesis. We find that Slug upregulation in angiogenic endothelial cells (EC) regulates an EMT-like suite of target genes, and suppresses Dll4-Notch signaling thereby p...
3 CitationsSource
#1Catherine Demos (Georgia Institute of Technology)H-Index: 3
#2Darian Williams (Georgia Institute of Technology)H-Index: 2
Last. Hanjoong Jo (Georgia Institute of Technology)H-Index: 73
view all 3 authors...
1 CitationsSource
#1Jin Ma (LUMC: Leiden University Medical Center)H-Index: 1
#2Gonzalo Sanchez-Duffhues (LUMC: Leiden University Medical Center)H-Index: 20
Last. Peter ten Dijke (LUMC: Leiden University Medical Center)H-Index: 78
view all 4 authors...
Endothelial to mesenchymal transition (EndMT) is a complex biological process that gives rise to cells with multipotent potential. EndMT is essential for the formation of the cardiovascular system during embryonic development. Emerging results link EndMT to the postnatal onset and progression of fibrotic diseases and cancer. Moreover, recent reports have emphasized the potential for EndMT in tissue engineering and regenerative applications by regulating the differentiation status of cells. Trans...
14 CitationsSource
#1Katerina Rohlenova (Katholieke Universiteit Leuven)H-Index: 13
#2Jermaine Goveia (Katholieke Universiteit Leuven)H-Index: 24
Last. Peter Carmeliet (Katholieke Universiteit Leuven)H-Index: 179
view all 39 authors...
Endothelial cell (EC) metabolism is an emerging target for anti-angiogenic therapy in tumor angiogenesis and choroidal neovascularization (CNV), but little is known about individual EC metabolic transcriptomes. By single-cell RNA sequencing 28,337 murine choroidal ECs (CECs) and sprouting CNV-ECs, we constructed a taxonomy to characterize their heterogeneity. Comparison with murine lung tumor ECs (TECs) revealed congruent marker gene expression by distinct EC phenotypes across tissues and diseas...
30 CitationsSource
#1Joanna Kalucka (Katholieke Universiteit Leuven)H-Index: 25
#2Laura P.M.H. de Rooij (Katholieke Universiteit Leuven)H-Index: 6
Last. Peter Carmeliet (Katholieke Universiteit Leuven)H-Index: 179
view all 35 authors...
Summary The heterogeneity of endothelial cells (ECs) across tissues remains incompletely inventoried. We constructed an atlas of >32,000 single-EC transcriptomes from 11 mouse tissues and identified 78 EC subclusters, including Aqp7+ intestinal capillaries and angiogenic ECs in healthy tissues. ECs from brain/testis, liver/spleen, small intestine/colon, and skeletal muscle/heart pairwise expressed partially overlapping marker genes. Arterial, venous, and lymphatic ECs shared more markers in more...
113 CitationsSource
#1Wei Feng (University of Pittsburgh)H-Index: 1
#2Lyuqin Chen (Stanford University)H-Index: 1
Last. Guang Li (University of Pittsburgh)H-Index: 15
view all 5 authors...
The endothelial cell exists in the whole body by lining the inner surface of vasculature and plays an important role in normal physiology and disease progressions. Each organ should have a heterogeneous population of endothelial cells, but these heterogeneities have not been systematically analyzed at single cell level. The Tabular Muris project profiled mouse single cells from 20 organs, which includes endothelial cells in 10 organs. Unsupervised analysis of these endothelial cells found they w...
15 CitationsSource
Cited By0