Integration of spatial and single-cell transcriptomic analysis uncovers cellular and molecular alterations in the hypertensive brain

AIMS: Hypertension is a major global health burden, and the central nervous system (CNS) plays a pivotal role in regulating blood pressure. However, the underlying cellular and molecular mechanisms remain incompletely understood. This study aimed to characterize the spatial and single-cell transcriptomic profiles of CNS regions implicated in hypertension. MATERIALS AND METHODS: Spatial transcriptomic sequencing and single-cell RNA sequencing were performed on the hypothalamus and medulla oblongata of spontaneously hypertensive rats and normotensive Wistar-Kyoto controls at 4 and 10 weeks of age. Transcriptomic findings were integrated with histological analyses and validated using human brain tissues. KEY FINDINGS: neurons, were characterized, exhibiting potential crosstalk with microglia, astrocytes, and oligodendrocytes. Further integrated analyses revealed a significant upregulation of Eno1 in hypertensive brains, implicating it in neural regulation of blood pressure. Findings in human samples were consistent with the results obtained from rats. SIGNIFICANCE: This study provides a comprehensive spatial transcriptomic atlas of the hypertensive brain, uncovering multidimensional molecular mechanisms underlying CNS-mediated blood pressure regulation. These results advance our understanding of neurogenic hypertension and may inform future diagnostic and therapeutic strategies.