Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells

Journal of Neuroinflammation
Qiong ZhouMartin L Doughty

Abstract

Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1β (interleukin-1 beta). We show TNFα and IL-1β induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1β effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic r...Continue Reading

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Citations

Nov 18, 2020·Advanced Healthcare Materials·Melissa CadenaSteven A Sloan

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Methods Mentioned

BETA
electrophoresis
PCR
reverse transcription PCR
Assay
flow cytometry
RNA-seq

Software Mentioned

PANTHER Classification System
Rad CFX Manager
XCell
GraphPad Prism
TopHat Alignment
DAVID
Cufflinks Assembly & DE
RAD
bcl2fastq2 Conversion
BIO

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