cellular architecture
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Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 15
Author(s):  
Veronica Sanchez ◽  
William Britt

The assembly of human cytomegalovirus (HCMV) and other herpesviruses includes both nuclear and cytoplasmic phases. During the prolonged replication cycle of HCMV, the cell undergoes remarkable changes in cellular architecture that include marked increases in nuclear size and structure as well as the reorganization of membranes in cytoplasm. Similarly, significant changes occur in cellular metabolism, protein trafficking, and cellular homeostatic functions. These cellular modifications are considered integral in the efficient assembly of infectious progeny in productively infected cells. Nuclear egress of HCMV nucleocapsids is thought to follow a pathway similar to that proposed for other members of the herpesvirus family. During this process, viral nucleocapsids must overcome structural barriers in the nucleus that limit transit and, ultimately, their delivery to the cytoplasm for final assembly of progeny virions. HCMV, similar to other herpesviruses, encodes viral functions that co-opt cellular functions to overcome these barriers and to bridge the bilaminar nuclear membrane. In this brief review, we will highlight some of the mechanisms that define our current understanding of HCMV egress, relying heavily on the current understanding of egress of the more well-studied α-herpesviruses, HSV-1 and PRV.


2021 ◽  
Vol 190 ◽  
pp. 38-56
Author(s):  
Alexandre Borges Marcelo ◽  
Flávio Alessandro Serrão Gonçalves ◽  
Fernando Pinhabel Marafão

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi2-vi2
Author(s):  
Julie Laffy ◽  
Masashi Nomura ◽  
Chen He ◽  
Lillian Bussema ◽  
Michal Slyper ◽  
...  

Abstract High-grade gliomas (HGG) with histone H3.3 G34R mutation are rare intractable tumours in the cerebral hemispheres that preferentially affect adolescents and young adults, but have unknown mechanisms of neuroanatomical specificity and tumourigenesis. Here, we performed single-nucleus RNA-sequencing of twenty patient samples, encompassing twelve tumours with G34R mutation and eight H3.3 wildtype HGGs, age- and location-matched. Both classes of HGG were heterogeneous, with malignant cells in multiple states, recapitulating neural and glial developmental trajectories. G34R HGG is distinguished by lack of malignant cells in the oligodendroglial lineage, and aberrant expression of neuronal programs superimposed over cellular states, resulting in hybrid glio-neuronal malignant programs. Singe-cell barcoding supports plasticity between cellular states in HGG with multiple possible transitions. CRISPR-correction of G34R in HGG models followed by scRNA-seq supports that the G34R mutation directly drives these aberrant programs. Our study provides a framework for studying the origin and tumourigenesis of paediatric gliomas.


2021 ◽  
Author(s):  
Fumihiro Watanabe ◽  
Ethan W. Hollingsworth ◽  
Jenna M. Bartley ◽  
Lauren Wisehart ◽  
Rahil Desai ◽  
...  

SummaryGlioblastoma stem cells (GSCs) are highly self-renewing, resistant to therapy, and are able to form lethal tumors1, 2. Tumor organoids have been developed to study tumor evolution1–4, and while GSCs can form organoids for glioblastoma multiforme, our understanding of their intrinsic immune, metabolic, genetic, and molecular programs is limited. To address this, we deeply characterized GSC-derived GBM organoids using a modified protocol (GBMOsm) from several patient-derived GSCs and found they develop into complex 3D tissues with unique self-organization, cancerous metabolic states, and burdensome genetic landscapes. We discovered that GBMOsc recapitulate the presence of two important cell populations thought to drive GBM progression, SATB2+ and HOPX+ progenitors. Despite being devoid of immune cells, transcriptomic analysis across GBMOsc revealed an immune-like molecular program, enriched in cytokine, antigen presentation and processing, T-cell receptor inhibitors, and interferon genes. We determined that SATB2+ and HOPX+ populations contribute to this immune and interferon landscape in GBM in vivo and GBMOsm. Our work deepens our understanding of the intrinsic molecular and cellular architecture of GSC-derived GBMO and defines a novel GBMOsc intrinsic immune-like program.


2021 ◽  
Author(s):  
Maxime Dhainaut ◽  
Samuel A Rose ◽  
Guray Akturk ◽  
Aleksandra Wroblewska ◽  
Eun Sook Park ◽  
...  

The cellular architecture of a tumor, particularly immune composition, has a major impact on cancer outcome, and thus there is an interest in identifying genes that control the tumor microenvironment (TME). While CRISPR screens are helping uncover genes regulating many cell-intrinsic processes, existing approaches are suboptimal for identifying gene functions operating extracellularly or within a tissue context. To address this, we developed an approach for spatial functional genomics called Perturb-map, which utilizes protein barcodes (Pro-Code) to enable spatial detection of barcoded cells within tissue. We show >120 Pro-Codes can be imaged within a tumor, facilitating spatial mapping of 100s of cancer clones. We applied Perturb-map to knockout dozens of genes in parallel in a mouse model of lung cancer and simultaneously assessed how each knockout influenced tumor growth, histopathology, and immune composition. Additionally, we paired Perturb-map and spatial transcriptomics for unbiased molecular analysis of Pro-Code/CRISPR lesions. Our studies found that in Tgfbr2 knockout lesions, the TME was converted to a mucinous state and T-cells excluded, which was concomitant with increased TGFb expression and pathway activation, suggesting Tgfbr2 loss on lung cancer cells enhanced suppressive effects of TGFb on the TME. These studies establish Perturb-map for functional genomics within a tissue at single cell-resolution with spatial architecture preserved.


2021 ◽  
Author(s):  
Ansam Sinjab ◽  
Guangchun Han ◽  
Warapen Treekitkarnmongkol ◽  
Kieko Hara ◽  
Patrick Brennan ◽  
...  

Author(s):  
Sigrid Hegna Ingvaldsen ◽  
Tora Sund Morken ◽  
Dordi Austeng ◽  
Olaf Dammann

AbstractResearch on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.


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