Cardiolipin released by microglia can act on neighboring glial cells to facilitate the uptake of amyloid-β (1–42)

Wenzel, Tyler J.; Murray, Taryn E.; Noyovitz, Benjamin; Narayana, Kamal; Gray, Taylor E.; Le, Jennifer; He, Jim; Simtchouk, Svetlana; Gibon, Julien; Alcorn, Jane; Mousseau, Darrell D.; Zandberg, Wesley F.; Klegeris, Andis

doi:10.1016/j.mcn.2022.103804

Cited by 8 publications

(3 citation statements)

References 39 publications

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“… BOs were grown as described in Wenzel et al (2023b) using EB formation media 5 for 24 h. (A) BOs derived from 86i and 87i cell lines exhibit all visual markers of proper development. (B–E) At day 90, the levels of housekeeping proteins TUBB3 ( p = 0.63 , U = 27), β-actin ( p = 0.57, U = 26), and GAPDH ( p = 0.48, U = 24) are consistently expressed at similar levels, (F) as are the levels of total protein ( p = 0.92, U = 237.5), indicating these cultures grow to similar sizes and complexities at similar rates.…”

Section: Resultsmentioning

confidence: 99%

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Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms

Wenzel,

Mousseau

2024

Front. Cell. Neurosci.

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Human brain organoids are emerging as translationally relevant models for the study of human brain health and disease. However, it remains to be shown whether human-specific protein processing is conserved in human brain organoids. Herein, we demonstrate that cell fate and composition of unguided brain organoids are dictated by culture conditions during embryoid body formation, and that culture conditions at this stage can be optimized to result in the presence of glia-associated proteins and neural network activity as early as three-months in vitro. Under these optimized conditions, unguided brain organoids generated from induced pluripotent stem cells (iPSCs) derived from male–female siblings are similar in growth rate, size, and total protein content, and exhibit minimal batch-to-batch variability in cell composition and metabolism. A comparison of neuronal, microglial, and macroglial (astrocyte and oligodendrocyte) markers reveals that profiles in these brain organoids are more similar to autopsied human cortical and cerebellar profiles than to those in mouse cortical samples, providing the first demonstration that human-specific protein processing is largely conserved in unguided brain organoids. Thus, our organoid protocol provides four major cell types that appear to process proteins in a manner very similar to the human brain, and they do so in half the time required by other protocols. This unique copy of the human brain and basic characteristics lay the foundation for future studies aiming to investigate human brain-specific protein patterning (e.g., isoforms, splice variants) as well as modulate glial and neuronal processes in an in situ-like environment.

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Section: Resultsmentioning

confidence: 99%

“…Human unguided BOs were generated as described elsewhere ( Lancaster and Knoblich, 2014 ; Wenzel et al, 2023b ). Briefly, iPSCs were incubated with 0.5 mM EDTA for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms

Wenzel,

Mousseau

2024

Front. Cell. Neurosci.

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“…Via immunized neural organoids, it has been discovered that microglia-derived cardiolipin enhances the endocytosis of Aβ by astrocytes and microglia themselves. The decrease in cardiolipin levels as one ages could potentially contribute to the onset of AD [ 87 ]. A decline in cardiolipin levels with aging may contribute to the pathogenesis of AD.…”

Section: Immunized Organoids In Neurodegenerative Diseasesmentioning

confidence: 99%

Integration of iPSC-Derived Microglia into Brain Organoids for Neurological Research

Mrza,

He,

Wang

2024

IJMS

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The advent of Induced Pluripotent Stem Cells (iPSCs) has revolutionized neuroscience research. This groundbreaking innovation has facilitated the development of three-dimensional (3D) neural organoids, which closely mimicked the intricate structure and diverse functions of the human brain, providing an unprecedented platform for the in-depth study and understanding of neurological phenomena. However, these organoids lack key components of the neural microenvironment, particularly immune cells like microglia, thereby limiting their applicability in neuroinflammation research. Recent advancements focused on addressing this gap by integrating iPSC-derived microglia into neural organoids, thereby creating an immunized microenvironment that more accurately reflects human central neural tissue. This review explores the latest developments in this field, emphasizing the interaction between microglia and neurons within immunized neural organoids and highlights how this integrated approach not only enhances our understanding of neuroinflammatory processes but also opens new avenues in regenerative medicine.

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Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus

Mishra,

Kumar,

Kaundal

2024

Mol Neurobiol

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Cardiolipin released by microglia can act on neighboring glial cells to facilitate the uptake of amyloid-β (1–42)

Cited by 8 publications

References 39 publications

Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms

Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms

Integration of iPSC-Derived Microglia into Brain Organoids for Neurological Research

Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus

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