Spatial transcriptomics reveals selective vulnerability of cardiac neural crest-derived glial cells in human myocardial infarction
- 1Anhui College of Traditional Chinese Medicine
Abstract
Cardiac neural crest-derived glial cells (CNGs) are recently identified glial cells that support cardiac autonomic innervation and maintain sympathetic-parasympathetic balance. Their fate in myocardial infarction (MI) is unknown. Here, we analyzed 16 human cardiac spatial transcriptomes spanning normal myocardium (n=4), infarct zone (n=5), border zone (inner, n=1; outer, n=3), and remote zone (n=3). CNGs (S100B+/GFAP+, CD68- spots) were selectively lost along a spatial gradient from healthy tissue to the infarct core (Spearman rho = -0.92, p = 4.5 x 10-7). Tissue-area-corrected analysis confirmed that CNG loss (26% retained in infarct zone vs. normal; p = 0.016) vastly exceeded overall tissue loss, indicating selective vulnerability rather than bulk tissue destruction. Mechanistically, oxidative phosphorylation (OXPHOS) activity in CNG-positive spots correlated positively with CNG survival (partial rho = 0.65, p = 0.009 after controlling for spot composition), consistent with a high metabolic demand underlying their ischemic sensitivity. Pyroptosis - but not ferroptosis or apoptosis - signatures correlated with CNG loss (partial rho = -0.67, p = 0.006). These findings identify CNGs as selectively vulnerable cellular components of the cardiac autonomic system in MI and nominate metabolic failure and pyroptosis as candidate mechanisms, providing a spatially resolved foundation for future mechanistic and interventional studies.
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BibTeX
@misc{xia2026spatial,
title = {{Spatial transcriptomics reveals selective vulnerability of cardiac neural crest-derived glial cells in human myocardial infarction}},
author = {X. Xia and Y. Ding and X. Zhao and Q. He and H. Zhang and Y. Gu and H. Bai and D. Pan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751638},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751638v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Spatial transcriptomics reveals selective vulnerability of cardiac neural crest-derived glial cells in human myocardial infarction
AU - X. Xia
AU - Y. Ding
AU - X. Zhao
AU - Q. He
AU - H. Zhang
AU - Y. Gu
AU - H. Bai
AU - D. Pan
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751638
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751638v1
AB - Cardiac neural crest-derived glial cells (CNGs) are recently identified glial cells that support cardiac autonomic innervation and maintain sympathetic-parasympathetic balance. Their fate in myocardial infarction (MI) is unknown. Here, we analyzed 16 human cardiac spatial transcriptomes spanning normal myocardium (n=4), infarct zone (n=5), border zone (inner, n=1; outer, n=3), and remote zone (n=3). CNGs (S100B+/GFAP+, CD68- spots) were selectively lost along a spatial gradient from healthy tissue to the infarct core (Spearman rho = -0.92, p = 4.5 x 10-7). Tissue-area-corrected analysis confirmed that CNG loss (26% retained in infarct zone vs. normal; p = 0.016) vastly exceeded overall tissue loss, indicating selective vulnerability rather than bulk tissue destruction. Mechanistically, oxidative phosphorylation (OXPHOS) activity in CNG-positive spots correlated positively with CNG survival (partial rho = 0.65, p = 0.009 after controlling for spot composition), consistent with a high metabolic demand underlying their ischemic sensitivity. Pyroptosis - but not ferroptosis or apoptosis - signatures correlated with CNG loss (partial rho = -0.67, p = 0.006). These findings identify CNGs as selectively vulnerable cellular components of the cardiac autonomic system in MI and nominate metabolic failure and pyroptosis as candidate mechanisms, providing a spatially resolved foundation for future mechanistic and interventional studies.
ER -