Multiparameter quantitative analyses of diagnostic cells in brain tissues from tuberous sclerosis complex.

Autor:	Arceneaux JS; Department of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, Meharry Medical College, Nashville, Tennessee, USA., Brockman AA; Department of Cell & Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA., Khurana R; Department of Cell & Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA., Chalkley ML; Department of Cell & Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA., Geben LC; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA., Krbanjevic A; Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Vestal M; Duke University Children's Hospital and Health Center, Durham, North Carolina, USA., Zafar M; Duke University Children's Hospital and Health Center, Durham, North Carolina, USA., Weatherspoon S; Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, Tennessee, USA.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA., Mobley BC; Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Ess KC; Department of Cell & Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Section of Child Neurology, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA., Ihrie RA; Department of Cell & Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.; Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jazyk:	angličtina
Zdroj:	Cytometry. Part B, Clinical cytometry [Cytometry B Clin Cytom] 2024 Jul 02. Date of Electronic Publication: 2024 Jul 02.
DOI:	10.1002/cyto.b.22194
Abstrakt:	The advent of high-dimensional imaging offers new opportunities to molecularly characterize diagnostic cells in disorders that have previously relied on histopathological definitions. One example case is found in tuberous sclerosis complex (TSC), a developmental disorder characterized by systemic growth of benign tumors. Within resected brain tissues from patients with TSC, detection of abnormally enlarged balloon cells (BCs) is pathognomonic for this disorder. Though BCs can be identified by an expert neuropathologist, little is known about the specificity and broad applicability of protein markers for these cells, complicating classification of proposed BCs identified in experimental models of this disorder. Here, we report the development of a customized machine learning pipeline (BAlloon IDENtifier; BAIDEN) that was trained to prospectively identify BCs in tissue sections using a histological stain compatible with high-dimensional cytometry. This approach was coupled to a custom 36-antibody panel and imaging mass cytometry (IMC) to explore the expression of multiple previously proposed BC marker proteins and develop a descriptor of BC features conserved across multiple tissue samples from patients with TSC. Here, we present a modular workflow encompassing BAIDEN, a custom antibody panel, a control sample microarray, and analysis pipelines-both open-source and in-house-and apply this workflow to understand the abundance, structure, and signaling activity of BCs as an example case of how high-dimensional imaging can be applied within human tissues. (© 2024 The Author(s). Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)
Databáze:	MEDLINE
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