single-cell RNA-seq of healthy (ctrl) and heart diseased (TAC) SCGs

Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet the underlying mechanism has remained enigmatic. Immunostaining of sympathetic axons in optically cleared pineal glands from humans and mice with cardiac disease revealed their substantial denervation compared to controls. Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the superior cervical ganglia (SCG), which responded to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and the selective loss of pineal gland-innervating neurons. Depletion of macrophages in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion. Our data identify the mechanism underlying the disturbance of diurnal rhythmicity in cardiac disease and suggest means for therapeutic intervention. SCGs from heart healthy and heart diseased mice were subjected to single-cell RNA-seq (10x Genomics).

心血管疾病常伴随生理性睡眠-觉醒周期紊乱与褪黑素水平降低，但其潜在机制始终不明。对心血管疾病患者及小鼠经光学透明化处理的松果体进行交感轴突免疫染色，结果显示与对照组相比，其交感轴突出现显著去神经支配。空间转录组、单细胞转录组、细胞核转录组及批量转录组测序将该缺陷溯源至颈上神经节（superior cervical ganglia, SCG）：该神经节在心血管疾病刺激下会出现炎性巨噬细胞聚集、纤维化，以及支配松果体的神经元选择性丢失。清除颈上神经节内的巨噬细胞，可阻断疾病相关的松果体去神经支配，并恢复生理性褪黑素分泌。本研究明确了心血管疾病中昼夜节律紊乱的潜在机制，并为治疗干预提供了潜在方向。本研究对健康小鼠与心血管疾病模型小鼠的颈上神经节进行了单细胞转录组测序（10x Genomics）。