小鼠下丘脑室旁核的综合单细胞 RNA-seq 图谱将转录组和功能类型联系起来。

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
J. B. Berkhout, D. Poormoghadam, C. Yi, A. Kalsbeek, O. C. Meijer, A. Mahfouz
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引用次数: 0

摘要

下丘脑室旁核(PVN)是一个高度复杂的脑区,通过神经内分泌信号、自主神经系统外流以及向其他脑区的投射,对体内平衡调节起着至关重要的作用。在过去几年中,下丘脑单细胞数据集极大地促进了人们对下丘脑多种细胞组成的了解。虽然 PVN 在功能上已被充分分类,但其分子分类目前仍不充分。为了解决这个问题,我们将各种 PVN 单细胞数据集整合到最近发表的下丘脑单细胞转录组图谱中,创建了详细的 PVN 转录组细胞类型图谱。此外,我们还根据相关文献、现有逆行追踪数据和 PVN 注射靶区的现有单细胞数据,对转录组细胞类型进行了功能分析。最后,我们通过免疫荧光染色验证了我们的研究结果。在我们的 PVN 图谱数据集中,我们发现了众所周知的不同神经肽类型,每种类型都由多种新型亚型组成。根据文献中描述的标记,我们确定 Avp-Tac1、Avp-Th、Oxt-Foxp1、Crh-Nr3c1 和 Trh-Nfib 是最重要的神经内分泌亚型。为了描述前自主神经功能群的特征,我们将脊髓投射前自主神经神经元的单细胞逆行追踪研究整合到我们的 PVN 图谱中。我们发现这些(交感神经前)神经元与我们数据集中的 Adarb2+ 神经元群聚集在一起。此外,我们还确定了迷走神经背侧运动核中 Crh、Oxt、Penk、Sst 和 Trh 受体的表达,迷走神经背侧运动核是副交感神经前区神经元投射的关键区域。最后,我们发现 Trh-Ucn3 和 Brs3-Adarb2 是一些向中心投射的神经元群。总之,我们的研究详细概述了小鼠 PVN 的转录组细胞类型,并首次尝试解决已识别群体的功能问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptomic and functional types

An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptomic and functional types

An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptomic and functional types

The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signaling, outflow of the autonomic nervous system, and projections to other brain areas. In the past years, single-cell datasets of the hypothalamus have contributed immensely to the current understanding of the diverse hypothalamic cellular composition. While the PVN has been adequately classified functionally, its molecular classification is currently still insufficient. To address this, we created a detailed atlas of PVN transcriptomic cell types by integrating various PVN single-cell datasets into a recently published hypothalamus single-cell transcriptome atlas. Furthermore, we functionally profiled transcriptomic cell types, based on relevant literature, existing retrograde tracing data, and existing single-cell data of a PVN-projection target region. Finally, we validated our findings with immunofluorescent stainings. In our PVN atlas dataset, we identify the well-known different neuropeptide types, each composed of multiple novel subtypes. We identify Avp-Tac1, Avp-Th, Oxt-Foxp1, Crh-Nr3c1, and Trh-Nfib as the most important neuroendocrine subtypes based on markers described in literature. To characterize the preautonomic functional population, we integrated a single-cell retrograde tracing study of spinally projecting preautonomic neurons into our PVN atlas. We identify these (presympathetic) neurons to cocluster with the Adarb2+ clusters in our dataset. Further, we identify the expression of receptors for Crh, Oxt, Penk, Sst, and Trh in the dorsal motor nucleus of the vagus, a key region that the pre-parasympathetic PVN neurons project to. Finally, we identify Trh-Ucn3 and Brs3-Adarb2 as some centrally projecting populations. In conclusion, our study presents a detailed overview of the transcriptomic cell types of the murine PVN and provides a first attempt to resolve functionality for the identified populations.

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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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