With all the data we have, we put together a summary of in vitro neuronal diversity that is programmed in this study, with the optimal condition to generate corresponding subtypes, the purity, and the enrichment of disease genes and ion channels as a resource for the community.

But are these iN subtypes functional? In collaboration with Hierlemann Lab, we used HD-MEA for electrophysiological measurements and found that patterned iNs are functionally and morphologically distinct! In addition, the morphological complexity is tightly linked with transcriptome maturation.

We experimentally validated the GRNs through TF knock-out or overexpression coupled with scRNA-seq. We found that regulon-hub TFs can be necessary and sufficient for specific neuron subtypes.

How does morphogen combinations contribute to this diversity? We inferred morphogen-centered gene regulatory networks (GRNs), identified combinatorial signaling cues and upregulated TFs underlying neuron subtype specification.

We designed a combinatorial patterning screen on top ot iNs. Using highly multiplexed scRNA-seq enabled by @parse.bsky.social, our screen gives rise to a wide spectrum of neurons, with identities mapped across forebrain, midbrain, hindbrain, spinal cord, sympathetic, and peripheral sensory neurons.

This is actually not surprising because pro-neural TFs such as NGN2 and ASCL1 are widely expressed across the developing nervous system. We started to think about the possibility of guiding iNs into associated lineages using morphogen combinations to program diverse neuron subtypes.

My postdoc work at Treutlein lab and @graycamplab.bsky.social with @jasperjanssens.bsky.social is out in @science.org ! We screen for neuron subtypes using pro-neural TFs + morphogen combinations + scRNA-seq and profiled over 700,000 cells in 480 conditions. www.science.org/doi/10.1126/...

Excited to announce that I will start my group at @crg.eu in Barcelona next April! We will decode and engineer cell fates using stem cell models, perturbation screening and single-cell multiomics. Looking forward to the new chapter ahead!