Unknown,Transcriptomics,Genomics,Proteomics

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The transcriptomics of SLC18A3 positive cells from arcuate nucleus of rats in different pubertal development stages.

ABSTRACT: Based on our spatial transcriptomics sequencing data, we observed solute carrier family 18 member A3 (SLC18A3) was specificially expressed in kisspeptin-expressed neurons in arcuate nucleus (ARC). SLC18A3 as a surface marker was used to examine the isolation of living kisspeptin-expressed neurons by flow cytometric (FACS) assay. Fresh isolated ARC nucleus tissues from female Sprague-Dawley rats in postnatal day (PND)-25, 35 and 45 (n=10 each group) were harvested, and processed single-cell suspension for FACS assay by SLC18A3. Here, we obtained two populations according to the cell size by FSC/SSC signals, and further harvested a small proportion of Slc18a3+ cells from hypothalamus of PND-25, 35 and 45. Smart-seq was conducted to detect the transcriptome of four population namely large Slc18a3+/- cells as well as small Slc18a3+/- cells.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Rattus norvegicus

SUBMITTER: Yihang Shen

PROVIDER: E-MTAB-10975 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Neurons in the arcuate nucleus (ARC) sense the fed/fasted state and regulate hunger. ARCAgRP neurons release GABA, NPY and the melanocortin-4 receptor (MC4R) antagonist, AgRP, and are activated by fasting1-4. When stimulated, they rapidly and potently drive hunger5,6. ARCPOMC neurons, in contrast, release the MC4R agonist, α-MSH, and are viewed as the counterpoint to ARCAgRP neurons. They are regulated in an opposite fashion and their activity leads to decreased hunger2,4,7. Together, ARCAgRP and ARCPOMC neurons constitute the ARC feeding center. Against this, however, is the finding that ARCPOMC neurons, unlike ARCAgRP neurons, fail to affect food intake over the timescale of minutes to hours following opto- or chemogenetic stimulation5,8. This suggests a rapidly acting component of the ARC satiety pathway is missing. Here, we show that excitatory ARC neurons identified by expression of vesicular glutamate transporter 2 (VGLUT2) and the oxytocin receptor, unlike ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRP projections on MC4R-expressing neurons in the paraventricular hypothalamus (PVHMC4R neurons), which are known to mediate satiety9. ARCPOMC neurons also send dense projections to the PVH. Importantly, the α-MSH they release post-synaptically potentiates glutamatergic synaptic activity onto PVHMC4R neurons – including that emanating from ARCVglut2 neurons. This suggests a means by which α-MSH can bring about satiety – via postsynaptic potentiation of this novel ARCVglut2 to PVHMC4R satiety circuit. Thus, while fast (GABA and NPY) and slow (AgRP) ARC hunger signals are delivered together by ARCAgRP neurons10,11, the temporally analogous satiety signals from the ARC, glutamate and α-MSH, are delivered separately by two parallel, interacting projections (from ARCVGLUT2 and ARCPOMC neurons). Discovery of this rapidly acting excitatory ARC → PVH satiety circuit, and its regulation by α-MSH, provides new insight into regulation of hunger/satiety.

Dataset Information

The transcriptomics of SLC18A3 positive cells from arcuate nucleus of rats in different pubertal development stages.

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