Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission

Marie A. Bentsen, Dylan M. Rausch, Zaman Mirzadeh, Kenjiro Muta, Jarrad M. Scarlett, Jenny M. Brown, Vicente Herranz-Pérez, Arian F. Baquero, Jonatan Thompson, Kimberly M. Alonge, Chelsea L. Faber, Karl J. Kaiyala, Camdin Bennett, Charles Pyke, Cecilia Ratner, Kristoffer L. Egerod, Birgitte Holst, Thomas H. Meek, Burak Kutlu, Yu Zhang, Thomas Sparso, Kevin L. Grove, Gregory J. Morton, Birgitte R. Kornum, José-Manuel García-Verdugo, Anna Secher, Rasmus Jorgensen, Michael W. Schwartz () and Tune H. Pers ()
Additional contact information
Marie A. Bentsen: University of Washington
Dylan M. Rausch: University of Copenhagen
Zaman Mirzadeh: Barrow Neurological Institute
Kenjiro Muta: University of Washington
Jarrad M. Scarlett: University of Washington
Jenny M. Brown: University of Washington
Vicente Herranz-Pérez: University of Valencia
Arian F. Baquero: Novo Nordisk Research Center Seattle, Inc.
Jonatan Thompson: University of Copenhagen
Kimberly M. Alonge: University of Washington
Chelsea L. Faber: University of Washington
Karl J. Kaiyala: University of Washington
Camdin Bennett: Novo Nordisk Research Center Seattle, Inc.
Charles Pyke: Novo Nordisk A/S
Cecilia Ratner: University of Copenhagen
Kristoffer L. Egerod: University of Copenhagen
Birgitte Holst: University of Copenhagen
Thomas H. Meek: Novo Nordisk Research Center Seattle, Inc.
Burak Kutlu: Novo Nordisk Research Center Seattle, Inc.
Yu Zhang: Novo Nordisk Research Center Seattle, Inc.
Thomas Sparso: Novo Nordisk A/S
Kevin L. Grove: Novo Nordisk Research Center Seattle, Inc.
Gregory J. Morton: University of Washington
Birgitte R. Kornum: University of Copenhagen
José-Manuel García-Verdugo: University of Valencia
Anna Secher: Novo Nordisk A/S
Rasmus Jorgensen: Novo Nordisk A/S
Michael W. Schwartz: University of Washington
Tune H. Pers: University of Copenhagen

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17720-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17720-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17720-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().