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

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Standard

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. / Bentsen, Marie A.; Rausch, Dylan M.; Mirzadeh, Zaman; Muta, Kenjiro; Scarlett, Jarrad M.; Brown, Jenny M.; Herranz-Pérez, Vicente; Baquero, Arian F.; Thompson, Jonatan; Alonge, Kimberly M.; Faber, Chelsea L.; Kaiyala, Karl J.; Bennett, Camdin; Pyke, Charles; Ratner, Cecilia; Egerod, Kristoffer L.; Holst, Birgitte; Meek, Thomas H.; Kutlu, Burak; Zhang, Yu; Sparso, Thomas; Grove, Kevin L.; Morton, Gregory J.; Kornum, Birgitte R.; García-Verdugo, José Manuel; Secher, Anna; Jorgensen, Rasmus; Schwartz, Michael W.; Pers, Tune H.

In: Nature Communications, Vol. 11, No. 1, 4458, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bentsen, MA, Rausch, DM, Mirzadeh, Z, Muta, K, Scarlett, JM, Brown, JM, Herranz-Pérez, V, Baquero, AF, Thompson, J, Alonge, KM, Faber, CL, Kaiyala, KJ, Bennett, C, Pyke, C, Ratner, C, Egerod, KL, Holst, B, Meek, TH, Kutlu, B, Zhang, Y, Sparso, T, Grove, KL, Morton, GJ, Kornum, BR, García-Verdugo, JM, Secher, A, Jorgensen, R, Schwartz, MW & Pers, TH 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

APA

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., ... Pers, T. H. (2020). Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. Nature Communications, 11(1), [4458]. https://doi.org/10.1038/s41467-020-17720-5

Vancouver

Bentsen MA, Rausch DM, Mirzadeh Z, Muta K, Scarlett JM, Brown JM et al. Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. Nature Communications. 2020;11(1). 4458. https://doi.org/10.1038/s41467-020-17720-5

Author

Bentsen, Marie A. ; Rausch, Dylan M. ; Mirzadeh, Zaman ; Muta, Kenjiro ; Scarlett, Jarrad M. ; Brown, Jenny M. ; Herranz-Pérez, Vicente ; Baquero, Arian F. ; Thompson, Jonatan ; Alonge, Kimberly M. ; Faber, Chelsea L. ; Kaiyala, Karl J. ; Bennett, Camdin ; Pyke, Charles ; Ratner, Cecilia ; Egerod, Kristoffer L. ; Holst, Birgitte ; Meek, Thomas H. ; Kutlu, Burak ; Zhang, Yu ; Sparso, Thomas ; Grove, Kevin L. ; Morton, Gregory J. ; Kornum, Birgitte R. ; García-Verdugo, José Manuel ; Secher, Anna ; Jorgensen, Rasmus ; Schwartz, Michael W. ; Pers, Tune H. / Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{e7ca34d4d87f422eb98dfbcf2188bc07,
title = "Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission",
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.",
author = "Bentsen, {Marie A.} and Rausch, {Dylan M.} and Zaman Mirzadeh and Kenjiro Muta and Scarlett, {Jarrad M.} and Brown, {Jenny M.} and Vicente Herranz-P{\'e}rez and Baquero, {Arian F.} and Jonatan Thompson and Alonge, {Kimberly M.} and Faber, {Chelsea L.} and Kaiyala, {Karl J.} and Camdin Bennett and Charles Pyke and Cecilia Ratner and Egerod, {Kristoffer L.} and Birgitte Holst and Meek, {Thomas H.} and Burak Kutlu and Yu Zhang and Thomas Sparso and Grove, {Kevin L.} and Morton, {Gregory J.} and Kornum, {Birgitte R.} and Garc{\'i}a-Verdugo, {Jos{\'e} Manuel} and Anna Secher and Rasmus Jorgensen and Schwartz, {Michael W.} and Pers, {Tune H.}",
year = "2020",
doi = "10.1038/s41467-020-17720-5",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission

AU - Bentsen, Marie A.

AU - Rausch, Dylan M.

AU - Mirzadeh, Zaman

AU - Muta, Kenjiro

AU - Scarlett, Jarrad M.

AU - Brown, Jenny M.

AU - Herranz-Pérez, Vicente

AU - Baquero, Arian F.

AU - Thompson, Jonatan

AU - Alonge, Kimberly M.

AU - Faber, Chelsea L.

AU - Kaiyala, Karl J.

AU - Bennett, Camdin

AU - Pyke, Charles

AU - Ratner, Cecilia

AU - Egerod, Kristoffer L.

AU - Holst, Birgitte

AU - Meek, Thomas H.

AU - Kutlu, Burak

AU - Zhang, Yu

AU - Sparso, Thomas

AU - Grove, Kevin L.

AU - Morton, Gregory J.

AU - Kornum, Birgitte R.

AU - García-Verdugo, José Manuel

AU - Secher, Anna

AU - Jorgensen, Rasmus

AU - Schwartz, Michael W.

AU - Pers, Tune H.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-17720-5

DO - 10.1038/s41467-020-17720-5

M3 - Journal article

C2 - 32895383

AN - SCOPUS:85090317380

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4458

ER -

ID: 249764529