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

Berkhout, J. B. (Leiden University Medical Center)
Poormoghadam, D. (Netherlands Institute for Neuroscience NIN - KNAW; Amsterdam UMC)
Yi, C. (Amsterdam UMC)
Kalsbeek, A. (Netherlands Institute for Neuroscience NIN - KNAW; Amsterdam UMC)
Meijer, O. C. (Leiden University Medical Center)
Mahfouz, A.M.E.T.A. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center)

2024

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.

hypothalamus
neuroendocrine
paraventricular
preautonomic
single-cell

http://resolver.tudelft.nl/uuid:093c0762-24b2-4e78-bd77-99076996de17

https://doi.org/10.1111/jne.13367

0953-8194

Journal of Neuroendocrinology, 36 (2)

Institutional Repository

journal article

© 2024 J. B. Berkhout, D. Poormoghadam, C. Yi, A. Kalsbeek, O. C. Meijer, A.M.E.T.A. Mahfouz