A Molecular Census of Arcuate Hypothalamus and Median Eminence Cell Types
By John N. Campbell, Evan Z. Macosko, Henning Fenselau, T. Pers, A. Lyubetskaya, Danielle E. Tenen, Melissa Goldman, A. Verstegen, J. Resch, Steven A. McCarroll and 3 more. 2017
730 citations recorded by the source corpus.
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.
Subfields: Cognitive Neuroscience, Endocrine and Autonomic Systems, Computational Biology & Bioinformatics, Neuroscience
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Citations in the corpus
- UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction (2018, methodology): “Mouse scRNA-seq [11] is proled gene expression data for 20,921 cells from an adult mouse.”
- Understanding How Dimension Reduction Tools Work: An Empirical Approach to Deciphering t-SNE, UMAP, TriMAP, and PaCMAP for Data Visualization (2020, background): “…(The Smithsonian Institute, 2020; Coenen and Pearce, 2019), USPS (Hull, 1994), MNIST (LeCun et al., 2010), FMNIST (Xiao et al., 2017), Mouse scRNA-seq (Campbell et al., 2017), 20 NewsGroups (Lang, 1995), Flow cytometry (Belkina and Snyder-Cappione, 2017), and KDD Cup 99 (Stolfo et al., 2000).”
- Molecular, Spatial and Functional Single-Cell Profiling of the Hypothalamic Preoptic Region (2018, neutral): “The neuronal populations that we uncovered in the preoptic region also largely differed from cell clusters described in scRNA-seq studies of other hypothalamic areas (33, 70), perhaps suggesting a molecular and cellular distinctiveness of this brain area.”
- Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain (2018, neutral): “…gene expression studies have yielded cell-type classifications in the mouse cerebral cortex (Tasic et al., 2016; Zeisel et al., 2015), retina (Shekhar et al., 2016), hypothalamic arcuate nucleus (Campbell et al., 2017), entopeduncular nucleus (Wallace et al., 2017), and amygdala (Wu et al., 2017).”
- A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain (2018, methodology): “We generated cell suspensions from adult male mice (60 – 70 days old; C57Blk6/N) by adapting protocols from single-cell patch-clamp recording (Carter and Bean, 2009).”
- Semaglutide lowers body weight in rodents via distributed neural pathways. (2020, background): “Studies describe distinct populations of tanycytes around the third ventricle, which display significantly different gene expression patterns (36).”