J. B. Berkhout, D. Poormoghadam, C. Yi, A. Kalsbeek, O. C. Meijer, A. Mahfouz
{"title":"An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptomic and functional types","authors":"J. B. Berkhout, D. Poormoghadam, C. Yi, A. Kalsbeek, O. C. Meijer, A. Mahfouz","doi":"10.1111/jne.13367","DOIUrl":null,"url":null,"abstract":"<p>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 <i>Avp</i>-<i>Tac1</i>, <i>Avp</i>-<i>Th</i>, <i>Oxt</i>-<i>Foxp1</i>, <i>Crh</i>-<i>Nr3c1</i>, and <i>Trh</i>-<i>Nfib</i> 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 <i>Adarb2</i><sup>+</sup> clusters in our dataset. Further, we identify the expression of receptors for <i>Crh</i>, <i>Oxt</i>, <i>Penk</i>, <i>Sst</i>, and <i>Trh</i> in the dorsal motor nucleus of the vagus, a key region that the pre-parasympathetic PVN neurons project to. Finally, we identify <i>Trh</i>-<i>Ucn3</i> and <i>Brs3</i>-<i>Adarb2</i> 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.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13367","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroendocrinology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jne.13367","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.