Human induced pluripotent stem cell-derived microglia with a CX3CR1-V249I genetic variant exhibit dysfunctional phenotypes and modulate neuronal growth and function

The preprint operates within the dominant paradigm of using human induced pluripotent stem cells (hiPSCs) and CRISPR technology to model human diseases, specifically neurodegenerative diseases, in vitro. It also adheres to the paradigm of studying microglia and their role in neuroinflammation and neurodegeneration.

This research represents a classic example of normal science. It investigates a specific genetic variant (CX3CR1-V249I) within the accepted framework of microglial involvement in neurodegenerative diseases. The study uses established tools and techniques like hiPSCs, CRISPR, and various assays to explore the effects of this variant on microglial function. The research aims to refine existing knowledge about the role of CX3CR1 in microglial activity and its potential implications for neurodegenerative disease susceptibility. It does not challenge the existing paradigm but rather works within it to deepen our understanding of a specific mechanism.