A molecular census of arcuate hypothalamus and median eminence cell types

John N Campbell; Evan Z Macosko; Henning Fenselau; Tune H Pers; Anna Lyubetskaya; Danielle Tenen; Melissa Goldman; Anne M J Verstegen; Jon M Resch; Steven A McCarroll; Evan D Rosen; Bradford B Lowell; Linus T Tsai

doi:10.1038/nn.4495

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A molecular census of arcuate hypothalamus and median eminence cell types

Journal article

Open access

Peer reviewed

A molecular census of arcuate hypothalamus and median eminence cell types

John N Campbell, Evan Z Macosko, Henning Fenselau, Tune H Pers, Anna Lyubetskaya, Danielle Tenen, Melissa Goldman, Anne M J Verstegen, Jon M Resch, Steven A McCarroll, …

Nature neuroscience, Vol.20(3), pp.484-496

03/2017

DOI: 10.1038/nn.4495

PMCID: PMC5323293

PMID: 28166221

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http://europepmc.org/articles/pmc5323293?pdf=renderView

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Abstract

The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a new leptin-sensing neuron population, multiple agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) subtypes, and an orexigenic somatostatin neuron population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinct responses in AgRP and POMC neuron subtypes. Finally, integrating our data with human genome-wide association study data implicates two previously unknown neuron populations in the genetic control of obesity. This resource will accelerate biological discovery by providing insights into molecular and cell type diversity from which function can be inferred.

Genome-Wide Association Study

Peptide Fragments - metabolism

Orexins - metabolism

Arcuate Nucleus of Hypothalamus - metabolism

Ependymoglial Cells - metabolism

Male

Mice, Transgenic

Gene Expression Profiling

Agouti-Related Protein - metabolism

Pro-Opiomelanocortin - physiology

Obesity - metabolism

Leptin - physiology

Peptide Fragments - physiology

Pro-Opiomelanocortin - metabolism

Median Eminence - anatomy & histology

Animals

Arcuate Nucleus of Hypothalamus - anatomy & histology

Agouti-Related Protein - physiology

Female

Mice

Neurons - metabolism

Energy Metabolism - physiology

Median Eminence - metabolism

Somatostatin - metabolism

Details

Title: Subtitle: A molecular census of arcuate hypothalamus and median eminence cell types
Creators: John N Campbell - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Evan Z Macosko - Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Henning Fenselau - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Tune H Pers - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Anna Lyubetskaya - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Danielle Tenen - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Melissa Goldman - Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Anne M J Verstegen - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Jon M Resch - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Steven A McCarroll - Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Evan D Rosen - Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Bradford B Lowell - Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
Linus T Tsai - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.20(3), pp.484-496
DOI: 10.1038/nn.4495
PMID: 28166221
PMCID: PMC5323293
NLM abbreviation: Nat Neurosci
ISSN: 1097-6256
eISSN: 1546-1726
Publisher: United States
Grant note: R01 DK096010 / NIDDK NIH HHS R01 DK089044 / NIDDK NIH HHS R01 DK102173 / NIDDK NIH HHS R01 DK102170 / NIDDK NIH HHS P30 DK057521 / NIDDK NIH HHS R37 DK053477 / NIDDK NIH HHS R01 DK111401 / NIDDK NIH HHS R01 DK085171 / NIDDK NIH HHS R01 DK075632 / NIDDK NIH HHS F32 DK103387 / NIDDK NIH HHS P30 DK046200 / NIDDK NIH HHS R25 MH094612 / NIMH NIH HHS R01 DK071051 / NIDDK NIH HHS
Language: English
Date published: 03/2017
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984065855102771

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