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| Status |
Public on Jul 01, 2020 |
| Title |
Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 [bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the hypothalamus was recently identified as a key target for this effect. To investigate how FGF1 action in this brain area achieves this effect, we combined single-nucleeus RNA sequencing (RNA-seq) with single-cell and traditional RNA-seq to identify >70,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1, 5 and 42 after icv injection of either FGF1 or vehicle. In addition to robust transcriptomics effects on Agrp neurons, which persisted through Day 42, rapid inhibition of Agrp neurons by FGF1 was shown by both electrophysiology and cFos studies. This effect is predicted to increase hypothalamic melanocortin signaling, and we show that FGF1-induced diabetes remission is melanocortin-dependent, as it was prevented by either genetic or pharmacological blockade of central melanocortin receptors. Combined with dramatic transcriptional and morphological changes induced by icv FGF1 injection in tanycytes, astrocytes and oligodendrocytes, including increased cellular contacts between astrocytes and Agrp neurons, these findings implicate glial-neuron interactions as mediators of the sustained remission of diabetes induced by the hypothalamic action of FGF1 action.
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| Overall design |
bulk RNA-sequencing
|
| |
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| Contributor(s) |
Bentsen MA, Rausch DM, Pers TH, Schwartz MW |
| Citation(s) |
32895383, 34430821 |
| |
| Submission date |
Jun 30, 2020 |
| Last update date |
Aug 31, 2021 |
| Contact name |
Tune Hannes Pers |
| E-mail(s) |
tune.pers@sund.ku.dk
|
| Organization name |
University of Copenhagen
|
| Department |
Novo Nordisk Foundation Center for Basic Metabolic Research
|
| Lab |
Tune Pers
|
| Street address |
Blegdamsvej 3B
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (47)
|
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| This SubSeries is part of SuperSeries: |
| GSE153551 |
Transcriptomic Analysis Links the Response of Diverse Hypothalamic Cell Types to Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1 |
|
| Relations |
| BioProject |
PRJNA643221 |
| SRA |
SRP269367 |
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