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Cluster 136, mostly in the amygdala has only 152 cells compared to, for example 20.000 for cluster 133, so perhaps that makes it less reliable and more likely to be a fluke? Cluster 133 has the following dissections: V1C:62.92%, V2:17.60%, Pro:14.65%, M1C:2.37%, A1C:1.23%, Ig:0.32%...

Wow, thanks. Much appreciated! I noticed that cluster 133 (the yellow dot just below the significance threshold) is also upper-layer intratelencephalic neurons located in the cortex. I do wonder what distinguishes cluster 136 and 133 of IT cells from other ITs that don't come near the...

Thanks, so that might point to the same Intratelencephalic (IT) glutamergic neurons as mentioned above but using another database (of the motor cortex only).

Thanks, guess I was trying to read too much into it, namely whether it really points to eMSN or a particular process or group of genes on them. Cerebellum Regarding that other cell type, these are glutamergic neurons from the Seeker 2023 white matter database, so a bit of an unusual category...

Another clarification: Paolo's readme file says that these are "IDs of overlapping genes". So likely these are only the genes that overlap with the HEAL2 replication.

Am afraid this interpretation of the conditional plot on signal depth across the genome is not correct, because Paolo's supplementary material S5 lists only a couple of genes per cell type tested. These are likely the 'specifically expressed genes (SEGs)' discussed in section 2.6.3. So that...

This study (Anderson et al. 2020) tested a FOXP1 knockout model in mice. FOXP1 is a gene that is important in the development of the striatum and has been linked to autism and intellectual disability. The study found that deleting FOXP1 led to more 2-4 fold increases in eMSN. So the idea is...

Some useful links for the Belgian context of ME/CFS: https://www.me-gids.net/ https://12me.be/ https://www.millionsmissingbelgique.com/ https://www.wucb.be/

One caveat is that the eMSN data is relatively new, discovered in 2018 and included in the human brain atlas in 2023. So a lot of GWAS from other diseases might not have tested for this cell type yet. Perhaps if they did, it would be connected to a lot of brain diseases and behavioral traits...

Think it's worth looking into these other cell types as well. Seems like there's a link to splatter cells as well which are also poorly understood. I also have a question @tralfamadorian97: does the signal for Amygdala excitatory (Cluster419) point to the amygdala's intercalated cells. Cause...

Possibly, but their paper mapped out the entire brain, and their data is relevant for 100s of medical conditions. It wasn't focused on eMSN in particular; they just happened to find it when mapping the entire brain. But with eMSN being largely unknown and there being a connection to ME/CFS, I...

A clarification that I didn't notice before: the human atlas mentions that most eMSN only have DRD1. Those with both DRD1 and DRD2 were a regional specialization in the basal ganglia. EDIT: here's figure 2 form the supplementary material:

The next major data source is the brain atlas by Siletti et al. 2023. Transcriptomic diversity of cell types across the adult human brain - PubMed They did the same single-cell RNA sequencing of the brain but in 3 human donors. They found 461 clusters for cell types, but there were also 31...

On the topic of links to the striatum, next to eMSN, HTT, and GPR52, there's also TSHZ3, which was a significant hit in Paolo's meta-analysis (not DecodeME alone). A bit more speculative perhaps, but knockout experiments of these genes in mice found changes in corticostriatal glutamatergic...

Yes, but it also came up in DecodeME itself https://www.s4me.info/threads/genetics-chromosome-1-rabgap1l.45502/post-693850 It's in the RABGAP1L region, but given what we know now about eMSN , GPR52 might be a more likely candidate. From what I understand, it's a receptor that modulates...

PCDH8, which plays a role in synaptic reorganization and down-regulation of dendritic spines. PCDH8 Gene - GeneCards | PCDH8 Protein | PCDH8 Antibody It's on chromosome 13. We thought that the DecodeME signal there pointed to OLFM4, as it is closer, but the fibromyalgia GWAS also found a signal...

Zooming in on the Saunders et al. 2018 paper that discovered eMSN. Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain - PubMed This was a major study where they built a brain-wide cell atlas of mice by extracting tissue and profiling individual cells' RNA using...

Agree, although I think the evidence suggests these cells are likely to play a key role in ME/CFS pathology.

Some speculation about this: - Perhaps some eMSN are in close enough proximity and well enough connected (e.g. those in the nucleus accumbens) to influence the hypothalamus - Perhaps eMSN CRH has influences through the ventricles - Perhaps there is a middle-man that interprets the excess of CRH...

My guess is that a little bit of CRH stimulates production, a bit like seeing other footballers on the pitch as a sign that the game has started. But that too much CRH gives negative feedback as so often happens in biology, a bit like seeing too many football players on the pitch already, so you...