[NTR] neuromuscular junction myonucleus

[erebboah]

Preferred term label neuromuscular junction myonucleus

Synonyms synaptic myonucleus (synonym from PMID:15827115), post-synaptic myonucleus (synonym from PMID:30443220)

Definition A specialized nucleus in a multinucleated skeletal muscle cell located near the neuromuscular junction (NMJ). Expresses acetylcholine receptor subunit genes as well as Musk, Lrp4, Colq, and Etv5, which have established roles in NMJ development (PMID: 33311464).

Parent cell type term skeletal muscle fiber (CL_0008002)

Anatomical structure where the cell type is found skeletal muscle (UBERON:0001134)

Your ORCID https://orcid.org/0000-0003-2273-0189

Additional notes or concerns The neuromuscular junction myonuclei are technically sub-cellular, but I think this term is still appropriate for CL for the benefit of muscle researchers who typically do single nucleus RNA-seq in order to capture and analyze these specialized nuclei.

[ghost]

@erebboah, thank you for the issue. As you mention above, this term represents an organelle, a sub-cellular structure. It is therefore outside the scope of being assigned a CL ID. If you would like to request a term for a skeletal muscle fiber located specifically in some NMJ, that would be in scope. However, if you require a term to represent an organelle, the appropriate ontology would be the Gene Ontology (GO).

[dosumis]

My worry is that GO CC may also consider it out of scope .

A nucleus is unlike any other organelle given it's central role in determining cellular identity. Nature doesn't always follow the neat lines we draw to define scope. So, I think this an interestingly ambiguous case. I'm sure FBbt will face a similar issue with already differentiating nuclei in the Drosophila syncytial blastoderm.

Proposed plan: Request from GO. If they are not amenable, CL team to discuss whether we can support in some way.

[dosumis]

BTW - are there other specialised muscle nuclie for which there is a similar need/justification?

[emquardokus]

It looks like GO already has several types of nuclei, so I think there's a good chance to get this term in. For reference in GO:

• [ ] nucleus GO:0005634 http://www.ebi.ac.uk/ols4/ontologies/go/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FGO_0005634
• [ ] nucleus localization GO:0051647
• [ ] neuromuscular junction of skeletal muscle fiber GO:0098522

Suggestions for term addition from this paper: NMJ-localized myonuclei as they show a difference between these and other skeletal myonuclei

In this paper, they specifically mention: "Other myonuclei subsets included neuromuscular junction (NMJ)–localized skeletal muscle myonuclei" @dosumis this is coming from consortia: HCA: Aviv Regev et al, Kristin Ardlie (GTEx); also worth noting that Cellular Senescence Network (SenNet) Program (NIH commonfund) is also heavily studying skeletal muscle). Worth referencing: Eraslan G, Drokhlyansky E, Anand S, Fiskin E, Subramanian A, Slyper M, Wang J, Van Wittenberghe N, Rouhana JM, Waldman J, Ashenberg O, Lek M, Dionne D, Win TS, Cuoco MS, Kuksenko O, Tsankov AM, Branton PA, Marshall JL, Greka A, Getz G, Segrè AV, Aguet F, Rozenblatt-Rosen O, Ardlie KG, Regev A. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function. Science. 2022 May 13;376(6594):eabl4290. doi: 10.1126/science.abl4290. Epub 2022 May 13. PMID: 35549429; PMCID: PMC9383269. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383269/pdf/nihms-1828607.pdf

[erebboah]

Thank you all for the prompt responses!

@bvarner-ebi That's true, the nucleus is an organelle. But many groups perform single-nucleus RNA-seq as a proxy for single-cell RNA-seq, even in non-muscle tissue, and identify cell types from the nuclear transcriptomes. Cell types can also be defined from snATAC-seq, which is always done on nuclei, not whole cells.

@dosumis There are specialized myonuclei of the myotendinous junction (MTJ) which are also annotated as a separate type in single-nucleus muscle studies due to localization at the MTJ and specific gene expression (PMID: 33311464, PMID: 33037211).

@emquardokus Thank you for tracking down the NMJ GO terms! The best term I found for MTJ myonuclei is muscle tendon junction, GO:0005927.

The GO terms are great, but I would love to be able to classify these nuclei with a CL ID for a standardized cell type annotation.

[dosumis]

Hi @erebboah - did you request from GO or should we ask for you?

[github-actions[bot]]

This issue has not seen any activity in the past 6 months; it will be closed automatically in one year from now if no action is taken.

[dosumis]

@erebboah - Apologies for the delay. We have requested this term from GO https://github.com/geneontology/go-ontology/issues/28211

If they do not accept it, we will add to CL instead.

Many thanks for your patience.