Histological Studies of the Ventricular–Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche

Brockman, Asa; Mobley, Bret C.; Ihrie, Rebecca A.

doi:10.1369/00221554211032003

Cited by 14 publications

(12 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the number of cells positive for the upper neural markers appears to be reduced, the organoids still maintain a cellular density similar to control. Further analysis of these organoids at later times of maturation using single cell RNA-sequencing (Kanton et al, 2019;Velasco et al, 2019) or mass cytometry (Brockman et al, 2021;Leelatian et al, 2017) would be useful to identify the effects of the LS-associated mutations in cortical cell fate specification.…”

Section: Discussionmentioning

confidence: 99%

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis

et al. 2022

View full text Add to dashboard Cite

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used to study Leigh syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In the case examined here, beyond identifying lymphoid and myeloid cells using 4 markers, expression of PD-1 and its ligand PD-L1 is also needed to identify populations of cells likely to respond to immune checkpoint inhibitor therapies. Similarly, in stem and progenitor cell studies, a combination of 3 to 7 or more proteins may be required to finely distinguish the specific population of interest (11)(12)(13)(14)(15). For this number of parameters, cyclic immunohistochemistry can be a rapid and largely automated approach that can be performed on a large number of samples in parallel.…”

Section: Discussionmentioning

confidence: 99%

Alignment, Segmentation and Neighborhood Analysis in Cyclic Immunohistochemistry Data Using CASSATT

Brockman

Khurana

Bartkowiak

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Cyclic immunohistochemistry (cycIHC) uses sequential rounds of colorimetric immunostaining and imaging for quantitative mapping of location and number of cells of interest. In addition, cycIHC benefits from the speed and simplicity of brightfield microscopy for data collection, making the collection of entire tissue sections and slides possible at a trivial cost compared to other high dimensional imaging modalities. However, large cycIHC datasets (greater than 50 GB) currently require an expert data scientist to concatenate separate open-source tools for each step of image pre-processing, registration, and segmentation, or the use of proprietary software. Here, we present a unified and user-friendly pipeline for processing, aligning, and analyzing cycIHC data - Cyclic Analysis of Single-Cell Subsets and Tissue Territories (CASSATT). CASSATT registers scanned slide images across all rounds of staining, segments individual nuclei, and measures marker expression on each detected cell. Beyond straightforward single cell data analysis outputs, CASSATT explores the spatial relationships between cell populations. By calculating the logodds of interaction frequencies between cell populations within tissues and tissue regions, this pipeline helps users identify populations of cells that interact - or do not interact - at frequencies that are greater than those occurring by chance. It also identifies specific neighborhoods of cells based on the assortment of neighboring cell types that surround each cell in the sample. The presence and location of these neighborhoods can be compared across slides or within distinct regions within a tissue. CASSATT was first tested using a newly generated cycIHC dataset consisting of six GBM tissue sections processed through eight cycles of AEC based IHC staining. Further validation was completed on a previously published lung cancer tissue microarray dataset consisting of 107 cores processed through eighteen cycles of staining and imaging. CASSATT is a fully open-source workflow tool developed to process cycIHC data and will allow greater utilization of this powerful staining technique.

show abstract

“…Glioma tumors in contact with the ventricles are often more multifocal and can recur distally from the primary tumor. Therapeutic resistance, tumor aggressiveness, and shorter patient survival are all associated with tumors in contact with ventricles [28][29][30][31][32].…”

Section: The Accumulation Of 11 C-methionine By Glioblastoma Tumor Ce...mentioning

confidence: 99%

Glioblastoma and Methionine Addiction

Sowers

2022

IJMS

View full text Add to dashboard Cite

Glioblastoma is a fatal brain tumor with a bleak prognosis. The use of chemotherapy, primarily the alkylating agent temozolomide, coupled with radiation and surgical resection, has provided some benefit. Despite this multipronged approach, average patient survival rarely extends beyond 18 months. Challenges to glioblastoma treatment include the identification of functional pharmacologic targets as well as identifying drugs that can cross the blood-brain barrier. To address these challenges, current research efforts are examining metabolic differences between normal and tumor cells that could be targeted. Among the metabolic differences examined to date, the apparent addiction to exogenous methionine by glioblastoma tumors is a critical factor that is not well understood and may serve as an effective therapeutic target. Others have proposed this property could be exploited by methionine dietary restriction or other approaches to reduce methionine availability. However, methionine links the tumor microenvironment with cell metabolism, epigenetic regulation, and even mitosis. Therefore methionine depletion could result in complex and potentially undesirable responses, such as aneuploidy and the aberrant expression of genes that drive tumor progression. If methionine manipulation is to be a therapeutic strategy for glioblastoma patients, it is essential that we enhance our understanding of the role of methionine in the tumor microenvironment.

show abstract

Histological Studies of the Ventricular–Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche

Cited by 14 publications

References 150 publications

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis

Alignment, Segmentation and Neighborhood Analysis in Cyclic Immunohistochemistry Data Using CASSATT

Glioblastoma and Methionine Addiction

Contact Info

Product

Resources

About