scholarly journals Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

2020 ◽  
Vol 6 (31) ◽  
pp. eabc5801 ◽  
Author(s):  
David H. Brann ◽  
Tatsuya Tsukahara ◽  
Caleb Weinreb ◽  
Marcela Lipovsek ◽  
Koen Van den Berge ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Neuronal Cell ◽  
Cell Types ◽  
Cell Entry ◽  
Common Symptom ◽  
Supporting Cells ◽  
Odor Perception ◽  
Sustentacular Cells ◽  
Human Olfactory Mucosa ◽  
Human Primate

Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

scholarly journals Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

2020 ◽  
Author(s):  
David H. Brann ◽  
Tatsuya Tsukahara ◽  
Caleb Weinreb ◽  
Marcela Lipovsek ◽  
Koen Van den Berge ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Epithelium ◽  
Neuronal Cell ◽  
Cell Types ◽  
Cell Entry ◽  
Common Symptom ◽  
Supporting Cells ◽  
Odor Perception ◽  
Human Olfactory Mucosa ◽  
Human Primate

AbstractAltered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing revealed that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing and immunostaining demonstrated ACE2 expression in support cells, stem cells, and perivascular cells; in contrast, neurons in both the olfactory epithelium and bulb did not express ACE2 message or protein. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

scholarly journals The landscape of alternative polyadenylation in single cells of the developing mouse embryo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikram Agarwal ◽  
Sereno Lopez-Darwin ◽  
David R. Kelley ◽  
Jay Shendure
Keyword(s):  
Rna Binding ◽  
Developmental Stages ◽  
Single Cells ◽  
Neuronal Cell ◽  
Alternative Polyadenylation ◽  
Cell Types ◽  
Untranslated Regions ◽  
Mammalian Development ◽  
Translation Rate ◽  
Dynamic Landscape

Abstract3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.

scholarly journals Effects of taurolithocholate, a Ca2+-mobilizing agent, on cell Ca2+ in rat hepatocytes, human platelets and neuroblastoma NG108-15 cell line

1991 ◽  
Vol 273 (1) ◽  
pp. 153-160 ◽  
Author(s):  
J F Coquil ◽  
B Berthon ◽  
N Chomiki ◽  
L Combettes ◽  
P Jourdon ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Bile Acid ◽  
Cell Line ◽  
Rat Liver ◽  
Neuronal Cell ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Liver Cells ◽  
Human Platelets ◽  
Rat Liver Cells

The monohydroxy bile acid taurolithocholate permeabilizes the endoplasmic reticulum to Ca2+ in rat liver cells. To assess whether this action on the endoplasmic reticulum was restricted to this tissue, the effects of bile acid were investigated in two cell types quite unrelated to rat hepatocyte, namely human platelets and neuronal NG108-15 cell line. The results showed that taurolithocholate (3-100 microM) had no effect on free cytosolic [Ca2+] in human platelets and NG108-15 cells. whereas it increased it from 180 to 520 nM in rat hepatocytes. In contrast, in cells permeabilized by saponin, taurolithocholate initiated a profound release of the stored Ca2+ from the internal Ca2+ pools in the three cell types. The bile acid released 90% of the Ca2+ pools, with rate constants of about 5 min-1 and half-maximal effects at 15-30 microM. The results also showed that, in contrast with liver cells, which displayed an influx of [14C]taurolithocholate of 2 nmol/min per mg, human platelets and the neuronal cell line appeared to be resistant to [14C]taurolithocholate uptake. The influx measured in these latter cells was about 100-fold lower than in rat liver cells. Taken together, these data suggest that human platelets and NG108-15 cells do not possess the transport system for concentrating monohydroxy bile acids into cells. However, they show that human platelets and neuronal NG108-15 possess, in common with liver cells, the intracellular system responsible for taurolithocholate-mediated Ca2+ release from internal stores.

scholarly journals Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

2007 ◽  
Vol 192 (3) ◽  
pp. 605-614 ◽  
Author(s):  
Fang Cai ◽  
Armen V Gyulkhandanyan ◽  
Michael B Wheeler ◽  
Denise D Belsham
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Cell Model ◽  
Neuronal Cell ◽  
Cell Types ◽  
Glucose Sensing ◽  
Protein Kinase Activity ◽  
Energy Status ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

Ultrastructure of the lophophoral tentacles in the genus Phoronis (Phoronida, Lophophorata)

1993 ◽  
Vol 71 (9) ◽  
pp. 1861-1868 ◽  
Author(s):  
F. Pardos ◽  
C. Roldán ◽  
J. Benito ◽  
A. Aguirre ◽  
I. Fernández
Keyword(s):  
Cell Types ◽  
Point Of View ◽  
Sensory Cells ◽  
Blood Capillary ◽  
Supporting Cells ◽  
Connective Tissue Layer ◽  
Hollow Structures ◽  
Building Activities ◽  
Abundance And Distribution ◽  
Epidermal Gland

The lophophoral tentacles of two phoronids, Phoronis psammophila and Phoronis hippocrepia, are described from an ultrastructural point of view. The tentacles are hollow structures, with an epidermis exhibiting supporting cells, sensory cells, and four types of gland cells, A, B1, B2, B3. The epidermis rests on a connective tissue layer, tubular in shape, enclosing a coelomic space lined by myoepithelial mesothelium (peritoneum). There is a single blood capillary in the tentacular coelomic cavity, attached to the frontal face of the tentacle, with contractile walls derived from the peritoneum. Both erythrocytes and amoebocyte-like cells occur inside the capillary. Differences between the tentacles of these two species and those of Phoronis australis, whose structure is already known, mainly concern the abundance and distribution of the epidermal gland cell types and are related to the burrowing and tube-building activities of these animals in different substrata.

Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

2021 ◽  
Author(s):  
Shachar Sherman ◽  
Koichi Kawakami ◽  
Herwig Baier
Keyword(s):  
Visual Information ◽  
Visual Stimulation ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Vertebrate Brain ◽  
Relative Contribution ◽  
Retinal Input ◽  
And Migration ◽  
The Brain

The brain is assembled during development by both innate and experience-dependent mechanisms1-7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7-9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11-16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.

scholarly journals A Deep Learning Approach for the Classification of Neuronal Cell Types

2018 ◽  
Author(s):  
Alessio P. Buccino ◽  
Torbjorn V. Ness ◽  
Gaute T. Einevoll ◽  
Gert Cauwenberghs ◽  
Philipp D. Hafliger
Keyword(s):  
Deep Learning ◽  
Neuronal Cell ◽  
Cell Types ◽  
Learning Approach
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