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Nat Neurosci DOI:10.1038/nn.4495

A molecular census of arcuate hypothalamus and median eminence cell types.

Publication TypeJournal Article
Year of Publication2017
AuthorsCampbell, JN, Macosko, EZ, Fenselau, H, Pers, TH, Lyubetskaya, A, Tenen, D, Goldman, M, Verstegen, AMJ, Resch, JM, McCarroll, SA, Rosen, ED, Lowell, BB, Tsai, LT
JournalNat Neurosci
Volume20
Issue3
Pages484-496
Date Published2017 Mar
ISSN1546-1726
KeywordsAgouti-Related Protein, Animals, Arcuate Nucleus of Hypothalamus, Energy Metabolism, Ependymoglial Cells, Female, Gene Expression Profiling, Genome-Wide Association Study, Leptin, Male, Median Eminence, Mice, Mice, Transgenic, Neurons, Obesity, Orexins, Peptide Fragments, Pro-Opiomelanocortin, Somatostatin
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.

DOI10.1038/nn.4495
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28166221?dopt=Abstract

Alternate JournalNat. Neurosci.
PubMed ID28166221
PubMed Central IDPMC5323293
Grant ListR01 DK085171 / DK / NIDDK NIH HHS / United States
R01 DK089044 / DK / NIDDK NIH HHS / United States
R01 DK096010 / DK / NIDDK NIH HHS / United States
R37 DK053477 / DK / NIDDK NIH HHS / United States
R25 MH094612 / MH / NIMH NIH HHS / United States
R01 DK071051 / DK / NIDDK NIH HHS / United States
R01 DK102173 / DK / NIDDK NIH HHS / United States
P30 DK046200 / DK / NIDDK NIH HHS / United States
P30 DK057521 / DK / NIDDK NIH HHS / United States
R01 DK075632 / DK / NIDDK NIH HHS / United States
R01 DK111401 / DK / NIDDK NIH HHS / United States
F32 DK103387 / DK / NIDDK NIH HHS / United States
R01 DK102170 / DK / NIDDK NIH HHS / United States