scholarly journals Re-convolving the compositional landscape of primary and recurrent glioblastoma using single nucleus RNA sequencing

2021 ◽  
Author(s):  
Osama Al-Dalahmah ◽  
Michael Argenziano ◽  
Deborah Boyett ◽  
Akshay Save ◽  
Aayushi Mahajan ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioma ◽  
Resection Margins ◽  
Brain Cells ◽  
Molecular Features ◽  
Compositional Approach ◽  
Glioma Recurrence ◽  
Single Nucleus ◽  
Cell Type Specific

Glioblastoma is an aggressive diffusely infiltrating neoplasm that spreads beyond surgical resection margins, where it intermingles with non-neoplastic brain cells. This complex tissue harboring infiltrating glioma and non-neoplastic brain cells is the origin of tumor recurrence. Thus, understanding the cellular and molecular features of the glioma margin is therapeutically and prognostically important. Here, we used single-nucleus RNA sequencing (snRNAseq) of primary and recurrent glioma to define compositional tissue-states that correlate with radiographic and histopathologic features. We found that glioma cells can be clustered into proliferative, astrocyte-like/mesenchymal, and progenitor-like/proneural states in both the primary and post-treatment recurrence settings. We focused on non-neoplastic microenvironment cells including oligodendrocytes, myeloid cells, neurons, and astrocytes - the latter two are under-represented in single-cell RNAseq studies. Cell type-specific signatures of the astrocyte-like/mesenchymal glioma, and a subpopulation of non-neoplastic astrocytes correlated with poor prognosis, the latter correlated with glioma recurrence. Notably, astrocytes were enriched for metabolic and neurodegenerative gene signatures. Leveraging snRNAseq-derived compositional information, we define three tissue-states that correlate with radiographic localization of primary and recurrent glioma. Our findings define a compositional approach to the glioma microenvironment and reveal prognostically and anatomically relevant features paving the way to new mechanistic and therapeutic discoveries.

P05.04 Reradiation by reccurent gliomas with VMAT (Volumetric Modulated Arc Therapy) technique- survival benefit

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii23-ii24
Author(s):  
M Theodorou ◽  
I Polycarpou
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Imaging Modality ◽  
Survival Rates ◽  
Volumetric Modulated Arc Therapy ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioma ◽  
Technique Survival ◽  
Glioma Recurrence

Abstract BACKGROUND Patients who have been treated with reirradiation for recurrent glioma reported survival benefits. Limited data are available for the outcomes after fractionated re-irradiation. This study aims to investigate whether re-irradiation of recurrent glioma with 45Gy dose can increase the overall survival of patients. MATERIAL AND METHODS A retrospective analysis of 35 patients re-irradiated for high-grade glioma recurrence between 2012 and 2020 was performed. All included patients met the following criteria: a) histopathological confirmation of primary brain cancer at initial diagnosis; b) a history of initial primary radiation; c) histological and/or imaging modality confirmation of recurrence. Outcome metrics included overall survival, prognostic factors for survival, and treatment-related toxicity. RESULTS After the end of re-irradiation the median overall survival was 11 months (95% confidence interval, 7–14 months). From the patients evaluated in the current study after the end of re-irradiation the progression free survival was 6 months (3.8 - 8 months) while after the end of first radiation was 13 months (8 - 17.9 months). Our findings suggest that re-irradiation might prolong survival rates. CONCLUSION Recurrent Glioblastoma WHO IV is associated with a median overall survival of less than a year and the majority of patients have profound tumor-related symptoms.The results of this study suggest that re-irradiation may prolong the overall survival.

scholarly journals EPCO-10. CHANGES IN ALTERNATIVE SPLICING AND ASSOCIATED NEOANTIGENS DUE TO THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii71-ii71
Author(s):  
Lin Wang ◽  
Karin Shamardani ◽  
Husam Babikir ◽  
Francisca Catalan ◽  
Takahide Nejo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Sequencing ◽  
Recurrent Glioblastoma ◽  
Surface Proteins ◽  
Sequencing Data ◽  
Cell Therapies ◽  
Effect Of Therapy ◽  
Cell Type Specific ◽  
Human Gbm ◽  
Splicing Patterns

Abstract Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in recurrent glioblastoma (GBM), despite this being the venue for most clinical trials. We profiled 29 primary-recurrent paired human GBM specimens via RNA sequencing and re-analyzed RNA-sequencing data from non-malignant human brain tissues. From these data, we reconstructed the landscape of AS in GBM through recurrence and contrasted that to isoforms observed in non-malignant brain. The AS events we identified were cross-referenced with single-cell GBM atlases to determine cell-type specific splicing patterns. From this we identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We found recurrent-specific isoforms of mitogen-activated kinase pathway genes which are expressed exclusively by GBM stem-like cells that enhance invasiveness. These studies shed light on the effect of therapy on AS and identify novel targets for emerging immunotherapies.

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 ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Molecular Taxonomy ◽  
Sequencing Analysis ◽  
Single Nucleus

Single-nucleus RNA-sequencing of human choriodecidua before and after the onset of labor

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e67
Author(s):  
Léa Chicoisne ◽  
Muriel Andrieu ◽  
Céline Bertholle ◽  
Vaarany Karunanithy ◽  
Brigitte Izac ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Before And After ◽  
Single Nucleus

scholarly journals Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205883 ◽  
Author(s):  
Joseph C. Mays ◽  
Michael C. Kelly ◽  
Steven L. Coon ◽  
Lynne Holtzclaw ◽  
Martin F. Rath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pineal Gland ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific ◽  
Mammalian Pineal Gland ◽  
Daily Patterns

scholarly journals Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas

2020 ◽  
Author(s):  
Luca Tosti ◽  
Yan Hang ◽  
Olivia Debnath ◽  
Sebastian Tiesmeyer ◽  
Timo Trefzer ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Human Pancreas ◽  
Single Nucleus

scholarly journals Single Cell, Single Nucleus and Spatial RNA Sequencing of the Human Liver Identifies Hepatic Stellate Cell and Cholangiocyte Heterogeneity

2021 ◽  
Author(s):  
Tallulah S Andrews ◽  
Jawairia Atif ◽  
Jeff C Liu ◽  
Catia T Perciani ◽  
Xue-Zhong Ma ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Human Liver ◽  
Stellate Cell ◽  
Parenchymal Cell ◽  
Cell Types ◽  
Cell Populations ◽  
Healthy Human ◽  
Single Nucleus

The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq). The addition of snRNA-seq enabled the characterization of interzonal hepatocytes at single-cell resolution, revealed the presence of rare subtypes of hepatic stellate cells previously only seen in disease, and detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and NK cells were only distinguishable using scRNA-seq, highlighting the importance of applying both technologies to obtain a complete map of tissue-resident cell-types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte and stellate cell populations by an independent spatial transcriptomics dataset and immunohistochemistry. Our study provides a systematic comparison of the transcriptomes captured by scRNA-seq and snRNA-seq and delivers a high-resolution map of the parenchymal cell populations in the healthy human liver.

EPCO-07. HYBRID NEURO-GLIAL CELLULAR ARCHITECTURE IN HIGH-GRADE GLIOMA DRIVEN BY H3-G34R MUTATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi2-vi2
Author(s):  
Julie Laffy ◽  
Masashi Nomura ◽  
Chen He ◽  
Lillian Bussema ◽  
Michal Slyper ◽  
...  
Keyword(s):  
Young Adults ◽  
Rna Sequencing ◽  
Developmental Trajectories ◽  
High Grade Glioma ◽  
Cerebral Hemispheres ◽  
High Grade ◽  
Malignant Cells ◽  
Aberrant Expression ◽  
Cellular Architecture ◽  
Single Nucleus

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.

Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney Fibrosis

2021 ◽  
pp. ASN.2020081143
Author(s):  
Yueh-An Lu ◽  
Chia-Te Liao ◽  
Rachel Raybould ◽  
Bnar Talabani ◽  
Irina Grigorieva ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Renal Fibrosis ◽  
High Performance ◽  
Genome Mapping ◽  
Gene Expression Signature ◽  
Metabolic Reprogramming ◽  
Normal Kidney ◽  
Kidney Fibrosis ◽  
Proximal Tubular ◽  
Single Nucleus

Background: Proximal tubular cells (PTCs) are the most abundant cell type in the kidney. PTCs are central to normal kidney function and to regeneration versus organ fibrosis following injury. This study used single-nucleus RNA sequencing (snRNA-seq) to describe the phenotype of PTCs in renal fibrosis. Methods: Kidneys were harvested from naïve mice and from mice with renal fibrosis induced by chronic aristolochic acid administration. Nuclei were isolated using Nuclei EZ Lysis buffer. Libraries were prepared on the 10X platform and snRNA-seq completed using the Illumina NextSeq 550 System. Genome mapping was carried out with high-performance computing. Results: A total of 23,885 nuclei were analysed. PTCs were found in five abundant clusters, mapping to S1, S1-2, S2, S2-cortical S3, and medullary S3 segments. Additional cell clusters ("new PTC clusters") were at low abundance in normal kidney and in increased number in kidneys undergoing regeneration/fibrosis following injury. These clusters exhibited clear molecular phenotypes, permitting labelling as proliferating, New-PT1, New-PT2, and (present only following injury) New-PT3. Each cluster exhibited a unique gene expression signature, including multiple genes previously associated with renal injury response and fibrosis progression. Comprehensive pathway analyses revealed metabolic reprogramming, enrichment of cellular communication and cell motility, and various immune activations in new PTC clusters. In ligand-receptor analysis, new PTC clusters promoted fibrotic signaling to fibroblasts and inflammatory activation to macrophages. Conclusion: These data identify unrecognized PTC phenotype heterogeneity and reveal novel PTCs associated with kidney fibrosis.

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