Neuroinflammatory astrocytes generated from cord blood-derived human induced pluripotent stem cells.
J Neuroinflammation
; 16(1): 164, 2019 Aug 09.
Article
em En
| MEDLINE
| ID: mdl-31395092
ABSTRACT
BACKGROUND:
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).METHODS:
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-1ß (interleukin-1 beta).RESULTS:
We show TNFα and IL-1ß 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-1ß effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity.CONCLUSION:
Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
/
Astrócitos
/
Mediadores da Inflamação
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Células-Tronco Pluripotentes Induzidas
/
Sangue Fetal
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article