ESPEYB16 1. Pituitary and Neuroendocrinology Basic Science: Single-cell Profiling the Hypothalamus (1 abstracts)
1.11. Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region
Moffitt JR , Bambah-Mukku D , Eichhorn SW , Vaughn E , Shekhar K , Perez JD , Rubinstein ND , Hao J , Regev A , Dulac C & Zhuang X
Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA dulac@fas.harvard.edu; zhuang@chemistry.harvard.edu
To read the full abstract: Science 2018;362(6416) eaau5324
The hypothalamus is a highly complex region, which receives many inputs from several other brain regions and also from the periphery. It is the site of synthesis of many neuropeptides that act as neurotransmitters or via the systemic circulation (in blood). Hypothalamic nuclei are typically defined by their exact anatomical location but also by their functions. The aim of this work was to create an annotated and spatially resolved atlas of the mouse hypothalamic preoptic region.
The authors combined two different but complementary approaches: single cell RNA sequencing (scRNA-seq) and a multiplexed fluorescence in situ hybridization (MERFISH) which detects individual RNA molecules with single-molecule FISH enabling trancriptome-scale RNA of individual cells in situ. In other words, the first method allows the classification of cells based on their gene expression profiles, whereas the second method defines cell populations based on their spatial organization in situ.
By profiling ~1 million cells, this work defined 70 neuronal clusters. Genes that discriminated between these neuronal clusters were enriched for neuropeptides and proteins involved in neuromodulator synthesis and transport. These clusters were enriched in genes previously reported to be involved in many physiological functions controlled by the preoptic region. One interesting feature was the confirmation that individual nuclei of the preoptic region were composed of multiple neuronal clusters. An intriguing result was the demonstration that GnRH neurons express Esr1 which encodes estradiol receptor alpha. This result contradicts many studies indicating that E1 acts on the GnRH neuronal network through Kisspeptin neurons. This work also confirmed the expression of aromatase in specific type of nuclei which leads to a cell-autonomous action of E2 or a paracrine effect.
Finally, the authors showed the sexual-dimorphism of many genes involved in specific behavioral traits.
Volume 16
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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