scholarly journals The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains

2021 ◽  
Vol 11 ◽  
Author(s):  
Rongrong Chen ◽  
Keer Wang ◽  
Jie Yu ◽  
Derek Howard ◽  
Leon French ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Spatial Distribution ◽  
Host Cells ◽  
Inhibitory Neurons ◽  
Middle Temporal Gyrus ◽  
Distribution Analysis ◽  
Cell Type ◽  
Type Distribution ◽  
The Brain ◽  
Human And Mouse

By engaging angiotensin-converting enzyme 2 (ACE2 or Ace2), the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades host cells and affects many organs, including the brain. However, the distribution of ACE2 in the brain is still obscure. Here, we investigated the ACE2 expression in the brain by analyzing data from publicly available brain transcriptome databases. According to our spatial distribution analysis, ACE2 was relatively highly expressed in some brain locations, such as the choroid plexus and paraventricular nuclei of the thalamus. According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in the human middle temporal gyrus and posterior cingulate cortex. A few ACE2-expressing nuclei were found in a hippocampal dataset, and none were detected in the prefrontal cortex. Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in the mouse brain was similar to that in the human brain. Thus, our results reveal an outline of ACE2/Ace2 distribution in the human and mouse brains, which indicates that the brain infection of SARS-CoV-2 may be capable of inducing central nervous system symptoms in coronavirus disease 2019 (COVID-19) patients. Potential species differences should be considered when using mouse models to study the neurological effects of SARS-CoV-2 infection.

The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain

2020 ◽  
Author(s):  
Rongrong Chen ◽  
Keer Wang ◽  
Jie Yu ◽  
Derek Howard ◽  
Leon French ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Spatial Distribution ◽  
Mouse Brain ◽  
Host Cells ◽  
Middle Temporal Gyrus ◽  
Distribution Analysis ◽  
Cell Type ◽  
Type Distribution ◽  
The Brain ◽  
Human And Mouse

AbstractBy engaging angiotensin-converting enzyme 2 (ACE2 or Ace2), the novel pathogenic SARS-coronavirus 2 (SARS-CoV-2) may invade host cells in many organs, including the brain. However, the distribution of ACE2 in the brain is still obscure. Here we investigated the ACE2 expression in the brain by analyzing data from publicly available brain transcriptome databases. According to our spatial distribution analysis, ACE2 was relatively highly expressed in some brain locations, such as the choroid plexus and paraventricular nuclei of the thalamus. According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in human middle temporal gyrus and posterior cingulate cortex. A few ACE2-expressing nuclei were found in a hippocampal dataset, and none were detected in the prefrontal cortex. Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in mouse brain was similar to that in the human brain. Thus, our results reveal an outline of ACE2/Ace2 distribution in the human and mouse brain, which indicates the brain infection of SARS-CoV-2 may be capable of inducing central nervous system symptoms in coronavirus disease 2019 (COVID-19) patients. Potential species differences should be considered when using mouse models to study the neurological effects of SARS-CoV-2 infection.

scholarly journals Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges

2019 ◽  
Vol 139 (2) ◽  
pp. 383-401 ◽  
Author(s):  
Shannon Shibata-Germanos ◽  
James R. Goodman ◽  
Alan Grieg ◽  
Chintan A. Trivedi ◽  
Bridget C. Benson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Dura Mater ◽  
Lymphatic Vessels ◽  
Amyloid Β ◽  
Lymphatic Endothelial Cells ◽  
Cell Type ◽  
Functional Conservation ◽  
Spherical Inclusions ◽  
Lymphatic Markers ◽  
The Brain

Abstract The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer’s disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.

scholarly journals Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2021
Author(s):  
Eun Seon Kim ◽  
Min-Tae Jeon ◽  
Kyu-Sung Kim ◽  
Suji Lee ◽  
Suji Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Cells ◽  
Spike Protein ◽  
Metabolic Function ◽  
Brain Endothelial Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Functional Deficits ◽  
Molecular Delivery ◽  
Pathological Mechanism ◽  
The Brain

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people’s lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain.

scholarly journals SURG-03. SPATIAL COORDINATES FROM GAMMA KNIFE RADIOSURGERY REVEAL PRIMARY CANCERS HAVE REGIONAL CNS TOPOGRAPHICAL DISTRIBUTION FOR BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i31-i31
Author(s):  
Josh Neman ◽  
Meredith Franklin ◽  
Zachary Madaj ◽  
Tim Triche ◽  
Gal Sadlik ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Brain Metastases ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Additive Models ◽  
Cerebellar Hemisphere ◽  
Distribution Analysis ◽  
Primary Tumors ◽  
Topographical Distribution ◽  
The Brain

Abstract Brain metastases arise in the central nervous system (CNS) following spread of circulating mesenchymal-type cells from primary tumors. While accumulating evidence underlines the importance of the neural niche in the establishment and progression of metastases, there still remains ambiguity over CNS anatomical spatial distribution from primary cancers. We evaluated 973 patients with brain metastases (breast, colorectal, lung, melanoma, renal) totaling 2,106 lesions treated from 1994–2015 with gamma knife radiosurgery at the University of Southern California Keck Medical Center for topographical distribution analysis. MRI images of the brain were taken and used in conjunction with the frame to precisely localize tumors and measure their size. Each tumor was given an x, y, and z-coordinate derived from the head frame that corresponded to its volumetric center within a 3-dimensional Cartesian field. Topographical analyses were conducted using logistic and multinomial spatial generalized additive models (GAM). For each cancer origin type we compared the observed brain metastases to set of randomly generated spatial observations to determine whether there were statistically significant localization patterns. Spatial pattern results show: 1) melanoma has highest probability to metastasize to the right frontal (74.5%, 95% confidence interval [Cl] = 63.6%- 85.4%) and to occipital lobe (72.4%, 95% Cl = 65.8%-78.9%), 2) while breast cancers have highest proclivity to metastasize to left cerebellar hemisphere (25%, 95% Cl=16.0%-34.1%) and brainstem (16.6%, 95% Cl= 10.8%-22.4%), 3) with lung tumors metastasizing to the left (23.7%, 95% Cl= 16.0–31.3%) and right parietal (24.7%, 95% Cl=16.7–32.8%), left temporal lobe (25.2%, 95% Cl=21.4%-29.1%). Colon and renal metastases show weak spatial patterns across the CNS. We conclude there is evidence of non-uniform spatial distribution of metastasis in the brain. These tumor-specific CNS topography patterns may underlie the ability of cancer cells to adapt to the regional neural microenvironments in order to facilitate colonization and establishment of metastasis.

Cartographic system for spatial distribution analysis of corneal endothelial cells

1994 ◽  
Vol 32 (4) ◽  
pp. 421-426 ◽  
Author(s):  
G. Corkidi ◽  
J. Márquez ◽  
M. García-Ruiz ◽  
S. Díaz-Cintra ◽  
E. Graue
Keyword(s):  
Endothelial Cells ◽  
Spatial Distribution ◽  
Distribution Analysis ◽  
Corneal Endothelial Cells

scholarly journals Parallel RNA and DNA analysis after Deep-sequencing (PRDD-seq) reveals cell type specific lineage patterns in human brain

2020 ◽  
Author(s):  
August Yue Huang ◽  
Pengpeng Li ◽  
Rachel E. Rodin ◽  
Sonia N. Kim ◽  
Yanmei Dou ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Cell Lineage ◽  
Neuronal Cell ◽  
Cell Types ◽  
Inhibitory Neurons ◽  
Cell Type ◽  
Cell Divisions ◽  
Excitatory Neurons ◽  
The Brain

AbstractElucidating the lineage relationships among different cell types is key to understanding human brain development. Here we developed Parallel RNA and DNA analysis after Deep-sequencing (PRDD-seq), which combines RNA analysis of neuronal cell types with analysis of nested spontaneous DNA somatic mutations as cell lineage markers, identified from joint analysis of single cell and bulk DNA sequencing by single-cell MosaicHunter (scMH). PRDD-seq enables the first-ever simultaneous reconstruction of neuronal cell type, cell lineage, and sequential neuronal formation (“birthdate”) in postmortem human cerebral cortex. Analysis of two human brains showed remarkable quantitative details that relate mutation mosaic frequency to clonal patterns, confirming an early divergence of precursors for excitatory and inhibitory neurons, and an “inside-out” layer formation of excitatory neurons as seen in other species. In addition our analysis allows the first estimate of excitatory neuron-restricted precursors (about 10) that generate the excitatory neurons within a cortical column. Inhibitory neurons showed complex, subtype-specific patterns of neurogenesis, including some patterns of development conserved relative to mouse, but also some aspects of primate cortical interneuron development not seen in mouse. PRDD-seq can be broadly applied to characterize cell identity and lineage from diverse archival samples with single-cell resolution and in potentially any developmental or disease condition.Significance StatementStem cells and progenitors undergo a series of cell divisions to generate the neurons of the brain, and understanding this sequence is critical to studying the mechanisms that control cell division and migration in developing brain. Mutations that occur as cells divide are known as the basis of cancer, but have more recently been shown to occur with normal cell divisions, creating a permanent, forensic map of the clonal patterns that define the brain. Here we develop new technology to analyze both DNA mutations and RNA gene expression patterns in single cells from human postmortem brain, allowing us to define clonal patterns among different types of human brain neurons, gaining the first direct insight into how they form.

scholarly journals The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors

2020 ◽  
Author(s):  
Moheb Ghobrial ◽  
Jason Charish ◽  
Shigeki Takada ◽  
Taufik Valiante ◽  
Philippe P. Monnier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Expression Pattern ◽  
Viral Entry ◽  
Fetal Brain ◽  
Brain Endothelial Cells ◽  
Peripheral Vasculature ◽  
Brain Vasculature ◽  
Interaction Partners ◽  
The Brain ◽  
Human And Mouse

ABSTRACTA large number of hospitalized COVID-19 patients show neurological symptoms such as ischemic- and hemorrhagic stroke as well as encephalitis, and SARS-CoV-2 can directly infect endothelial cells leading to endotheliitis across multiple vascular beds. These findings suggest an involvement of the brain- and peripheral vasculature in COVID-19, but the underlying molecular mechanisms remain obscure. To understand the potential mechanisms underlying SARS-CoV-2 tropism for brain vasculature, we constructed a molecular atlas of the expression patterns of SARS-CoV-2 viral entry-associated genes (receptors and proteases) and SARS-CoV-2 interaction partners in human (and mouse) adult and fetal brain as well as in multiple non-CNS tissues in single-cell RNA-sequencing data across various datasets. We observed a distinct expression pattern of the cathepsins B (CTSB) and -L (CTSL) - which are able to substitute for the ACE2 co-receptor TMPRSS2 - in the human vasculature with CTSB being mainly expressed in the brain vasculature and CTSL predominantly in the peripheral vasculature, and these observations were confirmed at the protein level in the Human Protein Atlas and using immunofluorescence stainings. This expression pattern of SARS-CoV-2 viral-entry associated proteases and SARS-CoV-2 interaction partners was also present in endothelial cells and microglia in the fetal brain, suggesting a developmentally established SARS-CoV-2 entry machinery in the human vasculature. At both the adult and fetal stages, we detected a distinct pattern of SARS-CoV-2 entry associated genes’ transcripts in brain vascular endothelial cells and microglia, providing a potential explanation for an inflammatory response in the brain endothelium upon SARS-CoV-2 infection. Moreover, CTSB was co-expressed in adult and fetal brain endothelial cells with genes and pathways involved in innate immunity and inflammation, angiogenesis, blood-brain-barrier permeability, vascular metabolism, and coagulation, providing a potential explanation for the role of brain endothelial cells in clinically observed (neuro)vascular symptoms in COVID-19 patients. Our study serves as a publicly available single-cell atlas of SARS-CoV-2 related entry factors and interaction partners in human and mouse brain endothelial- and perivascular cells, which can be employed for future studies in clinical samples of COVID-19 patients.

Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

1974 ◽  
Vol 32 ◽  
pp. 148-149
Author(s):  
D. E. Philpott ◽  
A. Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Salivary Gland ◽  
Carotid Artery ◽  
Basement Membrane ◽  
Coronary Vessels ◽  
Ruthenium Red ◽  
E Coli ◽  
Old Rats ◽  
The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

Spatial Distribution Analysis of Attributes of Rock Joints Using Geomathematical Methods.

1996 ◽  
Vol 112 (13) ◽  
pp. 907-914 ◽  
Author(s):  
Katsuaki KOIKE ◽  
Yoshifumi NOGUCHI ◽  
Hiroshi IWASAKI ◽  
Katsuhiko KANEKO
Keyword(s):  
Spatial Distribution ◽  
Rock Joints ◽  
Distribution Analysis

Niche Sharing in Intertidal Mollusks and Decapods in Rocky Shore of Easter Island

2019 ◽  
Vol 53 (5) ◽  
pp. 417-422
Author(s):  
P. De los Ríos ◽  
E. Ibáñez Arancibia
Keyword(s):  
Spatial Distribution ◽  
Negative Binomial Distribution ◽  
Binomial Distribution ◽  
Rocky Shore ◽  
Negative Binomial ◽  
Null Model ◽  
Easter Island ◽  
Published Data ◽  
Distribution Analysis ◽  
Field Works

Abstract The coastal marine ecosystems in Easter Island have been poorly studied, and the main studies were isolated species records based on scientific expeditions. The aim of the present study is to apply a spatial distribution analysis and niche sharing null model in published data on intertidal marine gastropods and decapods in rocky shore in Easter Island based in field works in 2010, and published information from CIMAR cruiser in 2004. The field data revealed the presence of decapods Planes minutus (Linnaeus, 1758) and Leptograpsus variegatus (Fabricius, 1793), whereas it was observed the gastropods Nodilittorina pyramidalis pascua Rosewater, 1970 and Nerita morio (G. B. Sowerby I., 1833). The available information revealed the presence of more species in data collected in 2004 in comparison to data collected in 2010, with one species markedly dominant in comparison to the other species. The spatial distribution of species reported in field works revealed that P. minutus and N. morio have aggregated pattern and negative binomial distribution, L. variegatus had uniform pattern with binomial distribution, and finally N. pyramidalis pascua, in spite of aggregated distribution pattern, had not negative binomial distribution. Finally, the results of null model revealed that the species reported did not share ecological niche due to competition absence. The results would agree with other similar information about littoral and sub-littoral fauna for Easter Island.

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