scholarly journals The molecular taxonomy of primate amygdala via single-nucleus RNA-sequencing analysis

2021 ◽  
Author(s):  
Lei Zhang ◽  
Yanyong Cheng ◽  
Shihao Wu ◽  
Yufeng Lu ◽  
Zhenyu Xue ◽  
...  
2020 ◽  
Author(s):  
Lei Zhang ◽  
Yanyong Cheng ◽  
Shihao Wu ◽  
Yufeng Lu ◽  
Zhenyu Xue ◽  
...  

ABSTRACTAmygdala is the central brain region governing emotional responses of mammals. However, the detailed molecular taxonomy of amygdala in higher mammals such as primates is still absent. Here we present the molecular taxonomy of amygdala in rhesus monkeys by single-cell RNA sequencing analysis. We found that there are five major cell types in primate amygdala, glutamatergic neurons, GABAergic neurons, astroglia, oligodendrocytes and oligodendrocyte progenitor cells (OPCs). Glutamatergic neurons in the primate amygdala exhibits a great diversity comparing to them in the rodent amygdala. In particular, GABAergic neurons in primate amygdala appeared to be quite unique and contain different cellular composition as them in rodent amygdala. The astroglia in primate amygdala contains two more subtypes comparing to astroglia in rodent amygdala. Taken together, although the evolutionary conservation, the molecular taxonomy study of primate amygdala provides critical insights for understanding the cellular architecture of the primate brain.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii34
Author(s):  
Macarena De La Fuente ◽  
Tulay Koru-Sengul ◽  
Deborah Heros ◽  
Feng Miao ◽  
Alain Fernandez Marrero ◽  
...  

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stevan D. Stojanović ◽  
Maximilian Fuchs ◽  
Chunguang Liang ◽  
Kevin Schmidt ◽  
Ke Xiao ◽  
...  

AbstractThe family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.


2020 ◽  
Vol 6 (29) ◽  
pp. eaba1773 ◽  
Author(s):  
Sangsin Lee ◽  
Ning Ding ◽  
Yidi Sun ◽  
Tanglong Yuan ◽  
Jing Li ◽  
...  

Cytosine base editors (CBEs) enable efficient cytidine-to-thymidine (C-to-T) substitutions at targeted loci without double-stranded breaks. However, current CBEs edit all Cs within their activity windows, generating undesired bystander mutations. In the most challenging circumstance, when a bystander C is adjacent to the targeted C, existing base editors fail to discriminate them and edit both Cs. To improve the precision of CBE, we identified and engineered the human APOBEC3G (A3G) deaminase; when fused to the Cas9 nickase, the resulting A3G-BEs exhibit selective editing of the second C in the 5′-CC-3′ motif in human cells. Our A3G-BEs could install a single disease-associated C-to-T substitution with high precision. The percentage of perfectly modified alleles is more than 6000-fold for disease correction and more than 600-fold for disease modeling compared with BE4max. On the basis of the two-cell embryo injection method and RNA sequencing analysis, our A3G-BEs showed minimum genome- and transcriptome-wide off-target effects, achieving high targeting fidelity.


2018 ◽  
Vol 13 ◽  
pp. 1-15 ◽  
Author(s):  
Anna M.L. Coenen-Stass ◽  
Helena Sork ◽  
Sole Gatto ◽  
Caroline Godfrey ◽  
Amarjit Bhomra ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e90157 ◽  
Author(s):  
Estefanía Tarazón ◽  
Esther Roselló-Lletí ◽  
Miguel Rivera ◽  
Ana Ortega ◽  
Maria Micaela Molina-Navarro ◽  
...  

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e67
Author(s):  
Léa Chicoisne ◽  
Muriel Andrieu ◽  
Céline Bertholle ◽  
Vaarany Karunanithy ◽  
Brigitte Izac ◽  
...  

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