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Human neuron subtype programming through combinatorial patterning with scSeq readouts

Lin, H.-C.; Janssens, J.; Kroell, A.-S.; Hornauer, P.; Santel, M.; Okamoto, R.; Karava, K.; Priouret, M.; Garcia, M. P.; Schroeter, M.; Camp, G.; Treutlein, B.

2023-12-13 bioengineering
10.1101/2023.12.12.571318 bioRxiv
Show abstract

Human neurons programmed through transcription factor (TF) overexpression model neuronal differentiation and neurological diseases. However, programming specific neuron types remains challenging. Here, we modulate developmental signaling pathways combined with TF overexpression to explore the spectrum of neuron subtypes generated from pluripotent stem cells. We screened 480 morphogen signaling modulations coupled with NGN2 or ASCL1/DLX2 induction using a multiplexed single-cell transcriptomic readout. Analysis of 700,000 cells identified diverse excitatory and inhibitory neurons patterned along the anterior-posterior and dorsal-ventral axes of neural tube development. We inferred signaling and TF interaction networks guiding differentiation of forebrain, midbrain, hindbrain, spinal cord, peripheral sympathetic and sensory neurons. Our approach provides a strategy for cell subtype programming and to investigate how cooperative signaling drives neuronal fate.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.