scholarly journals Neuroserpin expression during human brain development and in adult brain revealed by immunohistochemistry and single cell RNA sequencing

2019 ◽  
Vol 235 (3) ◽  
pp. 543-554 ◽  
Author(s):  
Istvan Adorjan ◽  
Teadora Tyler ◽  
Aparna Bhaduri ◽  
Samuel Demharter ◽  
Cintia Klaudia Finszter ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Rna Sequencing ◽  
Adult Brain ◽  
Human Brain Development ◽  
Single Cell Rna Sequencing

scholarly journals Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

2021 ◽  
Author(s):  
Ugomma C. Eze ◽  
Aparna Bhaduri ◽  
Maximilian Haeussler ◽  
Tomasz J. Nowakowski ◽  
Arnold R. Kriegstein
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Radial Glia ◽  
Cortical Development ◽  
Cell Types ◽  
Human Cortex ◽  
Early Stages ◽  
Human Brain Development ◽  
Neuroepithelial Cells

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing

Glia ◽  
2020 ◽  
Vol 68 (6) ◽  
pp. 1291-1303 ◽  
Author(s):  
Kelly Perlman ◽  
Charles P. Couturier ◽  
Moein Yaqubi ◽  
Arnaud Tanti ◽  
Qiao‐Ling Cui ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Progenitor Cells ◽  
Rna Sequencing ◽  
Developmental Trajectory ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Single Cell Rna Sequencing

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing

Cephalalgia ◽  
2018 ◽  
Vol 38 (13) ◽  
pp. 1976-1983 ◽  
Author(s):  
William Renthal
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Expression Profiles ◽  
Cell Types ◽  
Susceptibility Genes ◽  
Brain Cell ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Brain Cell Types

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

scholarly journals 973. Single-cell RNA Sequencing Analysis of Zika Virus Infection in Human Stem Cell-Derived Cerebral Organoids

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S33-S34
Author(s):  
Karen Ocwieja ◽  
Alexandra Stanton ◽  
Alexsia Richards ◽  
Jenna Antonucci ◽  
Travis Hughes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Zika Virus ◽  
Model Systems ◽  
Sequencing Analysis ◽  
Human Stem Cell ◽  
Zikv Infection ◽  
Single Cell Rna Sequencing

Abstract Background The molecular mechanisms underpinning the neurologic and congenital pathologies caused by Zika virus (ZIKV) infection remain poorly understood. One barrier has been the lack of relevant model systems for the developing human brain; however, thanks to advances in the stem cell field, we can now evaluate ZIKV central nervous system infections in human stem cell-derived cerebral organoids which recapitulate complex 3-dimensional neural architecture. Methods We apply Seq-Well—a simple, portable platform for massively parallel single-cell RNA sequencing—to characterize cerebral organoids infected with ZIKV. Using this sequencing method, and published transcriptional profiles, we identify multiple cellular populations in our organoids, including neuroprogenitor cells, intermediate progenitor cells, and terminally differentiated neurons. We detect and quantify host mRNA transcripts and viral RNA with single-cell resolution, defining transcriptional features of uninfected cells and infected cells. Results In this model of the developing brain, we identify preferred tropisms of ZIKV infection and pronounced effects on cell division, differentiation, and death. Our data additionally reveal differences in cellular populations and gene expression within organoids infected by historic and contemporary ZIKV strains from a variety of geographic locations. This finding might help explain phenotypic differences attributed to the viruses, including variable propensity to cause microcephaly. Conclusion Overall, our work provides insight into normal and diseased human brain development, and suggests that both virus replication and host response mechanisms underlie the neuropathology of ZIKV infection. Disclosures All Authors: No reported Disclosures.

scholarly journals The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna M. Jermakowicz ◽  
Matthew J. Rybin ◽  
Robert K. Suter ◽  
Jann N. Sarkaria ◽  
Zane Zeier ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Single Cell ◽  
Rna Sequencing ◽  
Ex Vivo ◽  
Adult Brain ◽  
Bet Inhibitor ◽  
Bet Inhibitors ◽  
Single Cell Rna Sequencing

AbstractBromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNA-sequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM.

scholarly journals COMP-16. COMPREHENSIVE TRANSCRIPTOMIC ANALYSIS OF SINGLE CELLS FROM RECURRENT AND PRIMARY GLIOBLASTOMA TO PREDICT CELL-TYPE SPECIFIC THERAPEUTICS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi64-vi64
Author(s):  
Robert Suter ◽  
Vasileios Stathias ◽  
Anna Jermakowicz ◽  
Alexa Semonche ◽  
Michael Ivan ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Tumor Heterogeneity ◽  
Drug Response ◽  
Adult Brain ◽  
Cell Populations ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific ◽  
Recurrent Gbm

Abstract Glioblastoma (GBM) remains the most common adult brain tumor, with poor survival expectations, and no new therapeutic modalities approved in the last decade. Our laboratories have recently demonstrated that the integration of a transcriptional disease signature obtained from The Cancer Genome Atlas’ GBM dataset with transcriptional cell drug-response signatures in the LINCS L1000 dataset yields possible combinatorial therapeutics. Considering the extreme intra-tumor heterogeneity associated with the disease, we hypothesize that the utilization of single-cell RNA-sequencing (scRNA-seq) of patient tumors will further strengthen our predictive model by providing insight on the unique transcriptomes of the cellular niches present within these tumors, and into the transcriptional dynamics of these same cellular niches. By sequencing single-cell transcriptomes from recurrent GBM tumors resected from patients at the University of Miami, and integrating our datasets with previously published scRNA-seq data from primary GBM tumors, we are able to gain additional insight into the differences between these clinical distinctions. We have analyzed the differential expression of kinases both across and within distinct cell populations of primary and recurrent GBM tumors. This transcriptional map of kinase expression represents the heterogeneity of potential targets within individual tumors and between recurrent and primary GBM. Additionally, by generating disease signatures unique to each cellular population, and integrating these with transcriptional drug-response signatures from LINCS, we are able to predict compounds to target specific cell populations within GMB tumors. Additional computational techniques such as RNA velocity analysis and cell cycle scoring elucidate temporal insights to further prioritize these cell-type specific therapeutics, and reveal the intra-cellular dynamics present within these tumors. Collectively, our studies suggest that we have developed a novel omics pipeline based on the single cell RNA-sequencing of individual GBM cells that addresses intra-tumor heterogeneity, and may lead to novel therapeutic combinations for the treatment of this incurable disease.

scholarly journals A survey of human brain transcriptome diversity at the single cell level

2015 ◽  
Vol 112 (23) ◽  
pp. 7285-7290 ◽  
Author(s):  
Spyros Darmanis ◽  
Steven A. Sloan ◽  
Ye Zhang ◽  
Martin Enge ◽  
Christine Caneda ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cortical Neurons ◽  
Cell Types ◽  
Type I ◽  
Neuronal Populations ◽  
Brain Transcriptome ◽  
Single Cell Rna Sequencing ◽  
Whole Transcriptome

The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

scholarly journals Spatial cell type composition in normal and Alzheimers human brains is revealed using integrated mouse and human single cell RNA sequencing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Travis S. Johnson ◽  
Shunian Xiang ◽  
Bryan R. Helm ◽  
Zachary B. Abrams ◽  
Peter Neidecker ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Brain Tissue ◽  
Cell Types ◽  
Brain Atlas ◽  
Cell Type ◽  
Cell Type Composition ◽  
Type Composition ◽  
Single Cell Rna Sequencing

Abstract Single-cell RNA sequencing (scRNA-seq) resolves heterogenous cell populations in tissues and helps to reveal single-cell level function and dynamics. In neuroscience, the rarity of brain tissue is the bottleneck for such study. Evidence shows that, mouse and human share similar cell type gene markers. We hypothesized that the scRNA-seq data of mouse brain tissue can be used to complete human data to infer cell type composition in human samples. Here, we supplement cell type information of human scRNA-seq data, with mouse. The resulted data were used to infer the spatial cellular composition of 3702 human brain samples from Allen Human Brain Atlas. We then mapped the cell types back to corresponding brain regions. Most cell types were localized to the correct regions. We also compare the mapping results to those derived from neuronal nuclei locations. They were consistent after accounting for changes in neural connectivity between regions. Furthermore, we applied this approach on Alzheimer’s brain data and successfully captured cell pattern changes in AD brains. We believe this integrative approach can solve the sample rarity issue in the neuroscience.

scholarly journals 80. SINGLE-CELL RNA-SEQUENCING OF HUMAN BRAIN REGIONS IDENTIFIES CELL TYPES AND STATES RELEVANT TO DISEASE

2021 ◽  
Vol 51 ◽  
pp. e83-e84
Author(s):  
Sherif Gerges ◽  
Melissa Goldman ◽  
Sabina Berretta ◽  
Steven McCarroll ◽  
Mark Daly
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Types ◽  
Brain Regions ◽  
Single Cell Rna Sequencing
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