Investigating Insulin's Role in Gene Comparisons of Microglia Ex Vivo and iMGLs 2.0 to Establish Ex Vivo Identity in In Vitro Models
Derrick Park
Mercersburg Academy, Mercersburg, USA
Publication date: November 4, 2024
Mercersburg Academy, Mercersburg, USA
Publication date: November 4, 2024
DOI: http://doi.org/10.34614/JIYRC202421
ABSTRACT
Microglia, immune cells that maintain homeostasis in the Central Nervous System, are imperative to study Neurodegenerative Diseases. However, the challenge of accessing microglia ex vivo has hindered the development of accurate microglia models. This study compares gene expressions between microglia ex vivo and induced microglia-like cells 2.0 (iMGLs 2.0) to evaluate the validity of microglia models. Data analysis was conducted to identify SALL1, a key regulator of microglial identity, and compare gene expression levels between microglia ex vivo and iMGLs 2.0. SALL1 expression was notably lower in iMGLs 2.0 compared to microglia ex vivo. An enrichment analysis was performed to find the transcription factor that controls SALL1 expression level, which revealed that NR4A1 activates SALL1, potentially through the IGF1R insulin pathway. A172 cells were treated with varying insulin concentrations to validate this further, showing that insulin enhanced NR4A1 and SALL1 expression. These findings suggest that treating iMGLs 2.0 with insulin can improve the resemblance of iMGLs 2.0 to microglia ex vivo, advancing in vitro models to be used in future neurodegenerative disease research.
Microglia, immune cells that maintain homeostasis in the Central Nervous System, are imperative to study Neurodegenerative Diseases. However, the challenge of accessing microglia ex vivo has hindered the development of accurate microglia models. This study compares gene expressions between microglia ex vivo and induced microglia-like cells 2.0 (iMGLs 2.0) to evaluate the validity of microglia models. Data analysis was conducted to identify SALL1, a key regulator of microglial identity, and compare gene expression levels between microglia ex vivo and iMGLs 2.0. SALL1 expression was notably lower in iMGLs 2.0 compared to microglia ex vivo. An enrichment analysis was performed to find the transcription factor that controls SALL1 expression level, which revealed that NR4A1 activates SALL1, potentially through the IGF1R insulin pathway. A172 cells were treated with varying insulin concentrations to validate this further, showing that insulin enhanced NR4A1 and SALL1 expression. These findings suggest that treating iMGLs 2.0 with insulin can improve the resemblance of iMGLs 2.0 to microglia ex vivo, advancing in vitro models to be used in future neurodegenerative disease research.
