Single-cell analysis of the aging female mouse hypothalamus
Kaitlyn H. Hajdarovic,Doudou Yu,Lexi-Amber Hassell,Shane A. Evans,Sarah Packer,Nicola Neretti,Ashley E. Webb +6 more
TLDR
In this paper , a single-nuclei RNA sequencing of 40,064 hypothalamic nuclei from young and aged female mice was performed to identify cell type-specific signatures of aging in neuronal subtypes.Abstract:
Abstract Alterations in metabolism, sleep patterns, body composition and hormone status are all key features of aging. While the hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors, little is known about the intrinsic features of hypothalamic aging. Here, we perform single-nuclei RNA sequencing of 40,064 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neuronal subtypes as well as astrocytes and microglia. We uncover changes in cell types critical for metabolic regulation and body composition and in an area of the hypothalamus linked to cognition. Our analysis also reveals an unexpected female-specific feature of hypothalamic aging: the master regulator of X inactivation, Xist , is elevated with age, particularly in hypothalamic neurons. Moreover, using machine learning, we show that levels of X chromosome genes and Xist itself, can accurately predict cellular age. This study identifies critical cell-specific changes of the aging hypothalamus in mammals and uncovers a potential marker of neuronal aging in females. read more
Citations
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Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection
Juan F. Quintana,Praveena Chandrasegaran,Matthew C. Sinton,Emma Briggs,Thomas D. Otto,Rhiannon Heslop,Calum Bentley-Abbot,Colin Loney,Luis de Lecea,Neil A. Mabbott,Annette MacLeod +10 more
TL;DR: In this article , single cell and spatial transcriptomics of the mouse brain were integrated to identify that glial responses triggered by infection are readily detected in the proximity to the circumventricular organs, including the lateral and 3rd ventricle.
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A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics
Haoyang Li,Juexiao Zhou,Zhongxiao Li,Siyuan Chen,Xingyu Liao,Bin Zhang,Ruochi Zhang,Yu Wang,Shiwei Sun,Xin Gao +9 more
TL;DR: In this paper , the authors benchmarked 18 existing methods resolving a cellular deconvolution task with 50 real-world and simulated datasets by evaluating the accuracy, robustness, and usability of the methods.
Journal ArticleDOI
Age-associated DNA methylation changes in Xenopus frogs
Marco Morselli,Ronan Bennett,Nikko-Ideen Shaidani,Marko E. Horb,Leonid Peshkin,Matteo Pellegrini +5 more
TL;DR: Clear evidence is presented that the aquatic vertebrate species Xenopus tropicalis displays clear patterns of age-associated changes in DNA methylation, which allows it to leverage the unique resources available for Xenopus to study howDNA methylation relates to other hallmarks of aging.
Journal ArticleDOI
Understanding the aging hypothalamus, one cell at a time
TL;DR: In this article , the authors summarize current knowledge about the contribution of hypothalamic functions to aging and suggest ways in which single-cell ‘omics technologies can be used to further understand the aging hypothalamus and its role in longevity.
Journal ArticleDOI
Single-cell RNA-based phenotyping reveals a pivotal role of thyroid hormone receptor alpha for hypothalamic development.
Varun K. A. Sreenivasan,Riccardo Dore,Julia Resch,Julia Maier,Carola Dietrich,Jan-Olav Henck,Saranya Balachandran,Jens Mittag,Malte Spielmann +8 more
TL;DR: In this paper , the authors used single-nucleus RNA sequencing to obtain an unbiased view on the importance of TRα1 for hypothalamic development and cellular diversity, and they found that defective trα1 signaling has surprisingly little effect on the development of hypothalamic neuronal populations, but it heavily affects hypothalamic oligodendrocytes.
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