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

Issued Date

2020-12-01

Resource Type

Article

ISSN

20411723

DOI

10.1038/s41467-020-17720-5

Other identifier(s)

2-s2.0-85090317380

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Communications. Vol.11, No.1 (2020)

Suggested Citation

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, Tune H. Pers Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. Nature Communications. Vol.11, No.1 (2020). doi:10.1038/s41467-020-17720-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/58938

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Title

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

Author(s)

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
 Tune H. Pers

Other Contributor(s)

Seattle Children's Hospital
 Institut Cavanilles de Biodiversitat i Biologia Evolutiva
 Københavns Universitet
 Novo Nordisk Inc.
 Faculty of Medicine, Ramathibodi Hospital, Mahidol University
 University of Washington, Seattle
 University of Copenhagen, Faculty of Health Sciences
 University of Washington, Medicine
 Novo Nordisk A/S
 Universidad Jaume I
 Barrow Neurological Institute
 Cytoki Pharma

Abstract

© 2020, The Author(s). 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Chemistry

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/58938

Collections

Scopus 2020