Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission
| Autor: | Vicente Herranz-Pérez, Camdin M. Bennett, Burak Kutlu, Zaman Mirzadeh, Thomas H. Meek, Karl J. Kaiyala, Gregory J. Morton, Tune H. Pers, Kristoffer L. Egerod, Chelsea L. Faber, Jarrad M. Scarlett, Cecilia Ratner, Birgitte Rahbek Kornum, Rasmus Jorgensen, Dylan M. Rausch, Anna Secher, Jenny M. Brown, Kevin L. Grove, Birgitte Holst, Kenjiro Muta, Jonatan J Thompson, Charles Pyke, Michael W. Schwartz, José Manuel García-Verdugo, Marie A. Bentsen, Kimberly M. Alonge, Yu Zhang, Thomas Sparsø, Arian F. Baquero |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood Glucose Leptin Male General Physics and Astronomy Cell Communication Fibroblast growth factor Stereotaxic Techniques Mice 0302 clinical medicine Dietary Sucrose Computational models Agouti-Related Protein RNA-Seq lcsh:Science Mice Knockout Neurons Multidisciplinary Receptors Melanocortin Remission Induction digestive oral and skin physiology Type 2 diabetes Recombinant Proteins Oligodendroglia medicine.anatomical_structure Hypothalamus Fibroblast Growth Factor 1 Receptor Melanocortin Type 4 Melanocortin Single-Cell Analysis hormones hormone substitutes and hormone antagonists Signal Transduction Cell signaling medicine.medical_specialty Cell type Science Biology Diet High-Fat General Biochemistry Genetics and Molecular Biology Article Diabetes Mellitus Experimental 03 medical and health sciences Gene expression analysis Internal medicine medicine Animals Humans Hypoglycemic Agents Melanocyte-Stimulating Hormones Injections Intraventricular Cell Nucleus General Chemistry FGF1 Oligodendrocyte Melanocortins 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Astrocytes Stereotaxic technique lcsh:Q Transcriptome 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Bentsen, M A, Rausch, D M, Mirzadeh, Z, Muta, K, Scarlett, J M, Brown, J M, Herranz-Pérez, V, Baquero, A F, Thompson, J, Alonge, K M, Faber, C L, Kaiyala, K J, Bennett, C, Pyke, C, Ratner, C, Egerod, K L, Holst, B, Meek, T H, Kutlu, B, Zhang, Y, Sparso, T, Grove, K L, Morton, G J, Kornum, B R, García-Verdugo, J M, Secher, A, Jorgensen, R, Schwartz, M W & Pers, T H 2020, ' Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission ', Nature Communications, vol. 11, no. 1, 4458 . https://doi.org/10.1038/s41467-020-17720-5 Nature Communications Repositori Universitat Jaume I Universitat Jaume I |
| DOI: | 10.1038/s41467-020-17720-5 |
| Popis: | 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 mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling. In rodent models of type 2 diabetes, sustained remission of hyperglycemia can be induced by FGF1 action in the mediobasal hypothalamus. Here, the authors show that FGF1-injection is followed by marked changes in glial cell populations and that the sustained glycemic response is dependent on intact melanocortin signaling. |
| Databáze: | OpenAIRE |
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