A molecular census of arcuate hypothalamus and median eminence cell types.
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.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
John N
JN
Campbell
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Evan Z
EZ
Macosko
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Henning
H
Fenselau
The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Tune H
TH
Pers
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Anna
A
Lyubetskaya
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Danielle
D
Tenen
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Melissa
M
Goldman
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Anne M J
AM
Verstegen
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Jon M
JM
Resch
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Steven A
SA
McCarroll
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Evan D
ED
Rosen
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.|Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Bradford B
BB
Lowell
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Linus T
LT
Tsai
D054369:Agouti-Related Protein / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000033:anatomy & histology* / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D063928:Ependymoglial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D020738:Leptin / Q000502:physiology; D008297:Male; D008473:Median Eminence / Q000033:anatomy & histology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000378:metabolism / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism
D054369:Agouti-Related Protein; D020738:Leptin; D000068797:Orexins; D010446:Peptide Fragments; C412618:agouti-related peptide, (Yc(CRFFNAFC)Y); D013004:Somatostatin; D011333:Pro-Opiomelanocortin