Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming.

Area of Science:

• Neuroscience
• Cell Biology
• Regenerative Medicine

Background:

• Understanding psychiatric and neurological illnesses is limited by the difficulty of accessing patient neurons.
• Existing in vitro models require improvement in terms of invasiveness, cost, and speed for obtaining reproducible neuronal cells.

Purpose of the Study:

• To present a novel protocol for transdifferentiating human circulating monocytes into neuronal-like cells.
• To characterize these monocyte-derived neuronal-like cells (MDNCs) and assess their potential as a model for neurological studies.
• To compare this new method with existing in vitro neuronal models.

Main Methods:

• Transdifferentiation of human circulating monocytes into neuronal-like cells within 20 days, without viral vectors or reprogramming.
• Comprehensive characterization of MDNCs using immunofluorescence, flow cytometry, qRT-PCR, single-cell mRNA sequencing, electrophysiology, and pharmacology.
• Assessment of MDNC response to dopamine and colchicine, and evaluation of differentiation reproducibility.

Main Results:

• MDNCs exhibited characteristics of early-stage human neurons, expressing key neuroprogenitor and neuronal genes and proteins.
• MDNCs demonstrated electrical activity and responded to pharmacological stimuli (dopamine, colchicine) similarly to native neurons.
• Consistent differentiation rates, arborizations, and dopamine receptor 1 expression were observed across multiple samples from the same individual, with an average differentiation efficiency of 11.9%.

Conclusions:

• The developed protocol provides a rapid, non-viral, and reproducible method to generate neuronal-like cells from human monocytes.
• MDNCs represent a valuable in vitro model for studying neuronal development and diseases, offering advantages over existing models.
• This approach facilitates research into neurological and psychiatric disorders by providing accessible, patient-derived neuronal models.