A molecular census of arcuate hypothalamus and median eminence cell types. 2017

John N Campbell, and Evan Z Macosko, and Henning Fenselau, and Tune H Pers, and Anna Lyubetskaya, and Danielle Tenen, and Melissa Goldman, and Anne M J Verstegen, and Jon M Resch, and Steven A McCarroll, and Evan D Rosen, and Bradford B Lowell, and Linus T Tsai
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008473 Median Eminence Raised area at the infundibular region of the HYPOTHALAMUS at the floor of the BRAIN, ventral to the THIRD VENTRICLE and adjacent to the ARCUATE NUCLEUS OF HYPOTHALAMUS. It contains the terminals of hypothalamic neurons and the capillary network of hypophyseal portal system, thus serving as a neuroendocrine link between the brain and the PITUITARY GLAND. Eminentia Mediana,Medial Eminence,Eminence, Medial,Eminence, Median,Eminences, Medial,Eminentia Medianas,Medial Eminences,Mediana, Eminentia,Medianas, Eminentia
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011333 Pro-Opiomelanocortin A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP). POMC,Pro-Opiocortin,ACTH-Endorphin Precursor,ACTH-beta-Lipotropin Precursor,Corticotropin-beta-Lipotropin Precursor,Endorphin-ACTH Precursor,Opiocortin,Pre-POMC,Pre-pro-opiocortin,Preproopiomelanocortin,Pro-ACTH-Endorphin,Pro-Opio-Melanocortin,Proopiocortin,Proopiomelanocortin,ACTH Endorphin Precursor,ACTH beta Lipotropin Precursor,Corticotropin beta Lipotropin Precursor,Endorphin ACTH Precursor,Pre POMC,Pre pro opiocortin,Pro ACTH Endorphin,Pro Opio Melanocortin,Pro Opiocortin,Pro Opiomelanocortin
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D005260 Female Females
D000068797 Orexins Neuropeptide hormones that play a role in regulating a variety of behavioral and physiological processes in response to motivational stimuli. Hypocretin,Orexin,Hypocretin-1,Hypocretin-2,Hypocretins,Orexin-A,Orexin-B,Hypocretin 1,Hypocretin 2,Orexin A,Orexin B

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