Thread by @KhodosevichLab

It’s comics time again! Glad to see our manuscript out in @NatureComms where we describe neuronal subtypes affected in temporal lobe #epilepsy and reveal a neuronal subtype-specific molecular phenotype.

nature.com/articles/s4146…

Here's a brief explanation of our findings 1/10

We used the surgically excised temporal lobe (TL) cortex from 9 individuals with epilepsy and compared against 10 non-epileptic controls. MRI of the TL showed epilepsy-associated abnormalities.
We processed >110,000 cells from these samples for #snRNAseq 2/10

We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected
3/10

The subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes 4/10

Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits 5/10

We confirmed this dysregulation of glutamate signalling by single molecule fluorescent in situ hybridization (smFISH). In particular, we show a strong upregulation of AMPA receptor auxiliary subunit CKAMP44 across cortical layers... 6/10

...as well as subunits of AMPA and NMDA glutamate receptors, GluRA (GRIA1 gene) and NR3A (GRIN3A gene), respectively 7/10

Finally, genes coding for proteins required for synthesis of GABA (major inhibitory neurotransmitter), GAD1 and GAD2, and cannabinoid receptor 1, CNR1, also showed a downregulation in distinct inhibitory interneuron subtypes 8/10

The rightful honors for this work go to @ulrichpfistere1, @PetukhovViktor, @samdemharter, our amazing collaborators in the clinic Lars Pinborg (@Rigshospitalet), Istvan Adorjan (@semmelweishu) and the lab @KharchenkoLab, Jakob von Engelhardt (@uni_mainz_eng) and @tunepers 9/10

To the individuals who donated tissue for this study: we are extremely grateful and hope to have contributed towards a better understanding of this condition

Thanks also to colleagues at @UCPH_BRIC and @Metabolcenter for discussions and a wonderful working environment 10/10

If you're wondering who's drawing these comics, you can find him on Facebook m.facebook.com/pg/KomardinKon… or Instagram: instagram.com/komardin_konst…