Primary Cell Culture of Live Neurosurgically Resected Aged Adult Human Brain Cells and Single Cell Transcriptomics

Spaethling, Jennifer M.; Na, Young-Ji; Lee, Jaehee; Ulyanova, Alexandra V.; Baltuch, Gordon H.; Bell, Thomas; Brem, Steven; Chen, H. Isaac; Dueck, Hannah; Fisher, Stephen; Garcia, Marcela P.; Khaladkar, Mugdha; Kung, David; Lucas, Timothy H.; O’Rourke, Donald M.; Stefanik, Derek; Wang, Jinhui; Wolf, John A.; Bartfai, Tamás; Grady, M. Sean; Sul, Jai‐Yoon; Kim, Junhyong; Eberwine, James

doi:10.1016/j.celrep.2016.12.066

Cited by 64 publications

(71 citation statements)

References 41 publications

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“…To determine whether we could use this same approach to evaluate heteroplasmy of single human mitochondrion, we analyzed mitochondria isolated from primary human brain cell cultures (Spaethling et al, 2017). These cultures were prepared from residual surgically removed brain tissue upon glioblastoma resection from the left frontal cortex of a 63 yr. old female subject (Patient Number 50).…”

Section: Resultsmentioning

confidence: 99%

Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

Morris

Zhu

et al. 2017

Cell Reports

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Summary A number of mitochondrial diseases arise from Single Nucleotide Variant (SNV) accumulation in multiple mitochondria. Here we present a method for identification of variants present at the single mitochondrion level in individual mouse and human neuronal cells allowing for extremely high resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high confidence variants in mouse and one in human that were present in multiple mitochondria across cells. The pattern of variation revealed by single mitochondrion data shows surprisingly pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci suggests inheritance of variants across generations resulting in Poisson jackpot lines with large SNV load. Comparison of human and mouse variants suggests that the two species might employ distinct modes of somatic segregation. Single mitochondrion resolution revealed mitochondria mutational dynamics that we hypothesize to affect risk probabilities for mutations reaching disease thresholds.

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Section: Resultsmentioning

confidence: 99%

Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

Morris

Zhu

et al. 2017

Cell Reports

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“…Gene expression studies of neurons and glial cells have contributed to our understanding of the variety of gene expression profiles that advance distinct functions in different cell types [133][134][135][136][137][138][139][140]. Microarray analyses of isolated astrocytes have identified particular transcription profiles in AD and related animal models [141,142].…”

Section: Astrocytopathymentioning

confidence: 99%

Astrogliopathy in Tauopathies

Ferrer

2018

Neuroglia

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Astrocytes are involved in many diseases of the central nervous system, not only as reactive cells to neuronal damage but also as primary actors in the pathological process. Astrogliopathy is a term used to designate the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Astrocytopathy is utilized to name non-reactive astrogliosis covering hypertrophy, atrophy and astroglial degeneration with loss of function in astrocytes and pathological remodeling, as well as senescent changes. Astrogliopathy and astrocytopathy are hallmarks of tauopathies-neurodegenerative diseases with abnormal hyper-phosphorylated tau aggregates in neurons and glial cells. The involvement of astrocytes covers different disease-specific types such as tufted astrocytes, astrocytic plaques, thorn-shaped astrocytes, granular/fuzzy astrocytes, ramified astrocytes and astrocytes with globular inclusions, as well as others which are unnamed but not uncommon in familial frontotemporal degeneration linked to mutations in the tau gene. Knowledge of molecular differences among tau-containing astrocytes is only beginning, and their distinct functional implications remain rather poorly understood. However, tau-containing astrocytes in certain conditions have deleterious effects on neuronal function and nervous system integrity. Moreover, recent studies have shown that tau-containing astrocytes obtained from human brain tauopathies have a capacity for abnormal tau seeding and spreading in wild type mice. Inclusive conceptions include a complex scenario involving neurons, glial cells and local environmental factors that potentiate each other and promote disease progression in tauopathies.

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“…Existing methods can be customized by the user by setting detailed normalization parameters. For example, we implement a modification of the DESeq method by making the inclusion criterion a user set parameter, making it more applicable to sparse expression matrices such as single cell RNA-Seq data [27]. …”

Section: Resultsmentioning

confidence: 99%

PIVOT: platform for interactive analysis and visualization of transcriptomics data

et al. 2018

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BackgroundMany R packages have been developed for transcriptome analysis but their use often requires familiarity with R and integrating results of different packages requires scripts to wrangle the datatypes. Furthermore, exploratory data analyses often generate multiple derived datasets such as data subsets or data transformations, which can be difficult to track.ResultsHere we present PIVOT, an R-based platform that wraps open source transcriptome analysis packages with a uniform user interface and graphical data management that allows non-programmers to interactively explore transcriptomics data. PIVOT supports more than 40 popular open source packages for transcriptome analysis and provides an extensive set of tools for statistical data manipulations. A graph-based visual interface is used to represent the links between derived datasets, allowing easy tracking of data versions. PIVOT further supports automatic report generation, publication-quality plots, and program/data state saving, such that all analysis can be saved, shared and reproduced.ConclusionsPIVOT will allow researchers with broad background to easily access sophisticated transcriptome analysis tools and interactively explore transcriptome datasets.Electronic supplementary materialThe online version of this article (10.1186/s12859-017-1994-0) contains supplementary material, which is available to authorized users.

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Primary Cell Culture of Live Neurosurgically Resected Aged Adult Human Brain Cells and Single Cell Transcriptomics

Cited by 64 publications

References 41 publications

Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

Astrogliopathy in Tauopathies

PIVOT: platform for interactive analysis and visualization of transcriptomics data

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