Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Commun. 2024 Mar 4;15(1):1966. doi: 10.1038/s41467-024-45907-7.
The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles and then used multiplexed error robust fluorescence in situ hybridization (MERFISH) to map them spatially. We sampled ~1 million cells across the dPnTg and defined the spatial distribution of over 120 neuronal subtypes. Our analysis identified an unpredicted high transcriptional diversity in this region and pinpointed the unique marker genes of many neuronal subtypes. We also demonstrated that many neuronal subtypes are transcriptionally similar between humans and mice, enhancing this study's translational value. Finally, we developed a freely accessible, GPU and CPU-powered dashboard ( http://harvard.heavy.ai:6273/ ) that combines interactive visual analytics and hardware-accelerated SQL into a data science framework to allow the scientific community to query and gain insights into the data.
“背侧脑桥”或“背侧脑桥被盖”（dPnTg）是脑干的一部分。它是一个复杂的、密集的区域，其核参与调节许多重要的功能。其中值得注意的是臂旁核、Kölliker 融合核、Barrington 核、蓝斑核以及背侧、背外侧和腹侧被盖核。在这项研究中，我们应用单细胞核 RNA 测序（snRNA-seq）根据其独特的转录谱来解析神经元亚型，然后使用多重纠错稳健荧光原位杂交（MERFISH）来对其进行空间定位。我们对 dPnTg 中的约 100 万个细胞进行了采样，并定义了 120 多种神经元亚型的空间分布。我们的分析在该区域中发现了意想不到的高度转录多样性，并确定了许多神经元亚型的独特标记基因。我们还表明，许多神经元亚型在人类和小鼠之间具有转录相似性，提高了这项研究的转化价值。最后，我们开发了一个免费的、GPU 和 CPU 驱动的仪表盘（http://harvard.heavy.ai:6273/），将交互式可视化分析和硬件加速的 SQL 结合到一个数据科学框架中，使科学界能够查询和深入了解数据。
