Spatial transcriptomics reveals selective vulnerability of cardiac neural crest-derived glial cells in human myocardial infarction

Recent studies have identified cardiac neural crest-derived glial cells (CNGs) as essential support cells for cardiac autonomic innervation and maintaining a balance between sympathetic and parasympathetic nervous systems. However, the fate of these cells during myocardial infarction (MI) remains unclear. To investigate this, researchers analyzed 16 spatial transcriptomes from human cardiac tissues, including normal myocardium, infarct zones, border zones, and remote zones.

The study found that CNGs (S100B+/GFAP+ spots without CD68) were selectively lost along a spatial gradient, moving from healthy tissue towards the infarct core (Spearman rho = -0.92, with a p-value of 4.5 x 10^-7). This loss was confirmed to be significantly greater than overall tissue loss when corrected for tissue area, with only 26% of CNGs retained in the infarct zone compared to normal tissue (p = 0.016). This indicates that CNG loss is a selective vulnerability rather than a result of widespread tissue destruction.

The researchers also discovered that CNG-positive spots had a positive correlation with oxidative phosphorylation (OXPHOS) activity (partial rho = 0.65, p = 0.009 after controlling for spot composition). This suggests that CNGs have a high metabolic demand, making them particularly sensitive to ischemia. Furthermore, CNG loss correlated with a pyroptosis signature (partial rho = -0.67, p = 0.006), but not with ferroptosis or apoptosis.

These findings reveal that CNGs are selectively vulnerable components of the cardiac autonomic system in MI, with metabolic failure and pyroptosis as potential mechanisms. The spatially resolved data provide a foundation for future mechanistic and interventional studies focusing on this unique population of glial cells.