Do microglia converge on a single activation state or maintain distinct profiles across myelopathy etiologies?

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Description

The debate highlighted fundamental disagreement about whether microglia show convergent vs. heterogeneous activation patterns in different myelopathies. This unresolved question is critical for understanding the mechanistic basis of overlapping clinical presentations and determining whether universal microglial targets exist.

Source: Debate session sess_SDA-2026-04-08-gap-pubmed-20260406-062111-db808ee9 (Analysis: SDA-2026-04-08-gap-pubmed-20260406-062111-db808ee9)

Resolution criteria

Gap closes when: (1) Single-nucleus RNA-seq of microglia from at least 3 human myelopathy etiologies (e.g., ALS, MS, SCI) with >= 20 donors per group identifies shared and disease-specific transcriptional modules by Seurat/Harmony clustering; and (2) the analysis demonstrates whether a single DAM-like state accounts for >= 60% of activated microglia across all etiologies (convergent model) or etiology-specific clusters are statistically separable (silhouette score >= 0.3); and (3) key protein-level markers of each cluster are validated by immunohistochemistry in tissue. Deliverable: public snRNA-seq dataset with clustering analysis and IHC validation panel.

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