1. The Human and Mouse Enteric Nervous System at Single-Cell Resolution.
- Author
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Drokhlyansky E, Smillie CS, Van Wittenberghe N, Ericsson M, Griffin GK, Eraslan G, Dionne D, Cuoco MS, Goder-Reiser MN, Sharova T, Kuksenko O, Aguirre AJ, Boland GM, Graham D, Rozenblatt-Rosen O, Xavier RJ, and Regev A
- Subjects
- Aging genetics, Aging metabolism, Animals, Circadian Clocks genetics, Colon cytology, Colon metabolism, Endoplasmic Reticulum, Rough genetics, Endoplasmic Reticulum, Rough metabolism, Endoplasmic Reticulum, Rough ultrastructure, Epithelial Cells metabolism, Female, Genetic Predisposition to Disease genetics, Humans, Ileum cytology, Ileum metabolism, Inflammation genetics, Inflammation metabolism, Intestinal Diseases genetics, Intestinal Diseases metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Transmission, Nervous System Diseases genetics, Nervous System Diseases metabolism, Neuroglia cytology, Neuroglia metabolism, Neurons cytology, Nissl Bodies genetics, Nissl Bodies ultrastructure, RNA, Messenger genetics, RNA-Seq, Ribosomes metabolism, Ribosomes ultrastructure, Stromal Cells metabolism, Enteric Nervous System cytology, Enteric Nervous System metabolism, Gene Expression Regulation, Developmental genetics, Neurons metabolism, Nissl Bodies metabolism, RNA, Messenger metabolism, Single-Cell Analysis methods
- Abstract
The enteric nervous system (ENS) coordinates diverse functions in the intestine but has eluded comprehensive molecular characterization because of the rarity and diversity of cells. Here we develop two methods to profile the ENS of adult mice and humans at single-cell resolution: RAISIN RNA-seq for profiling intact nuclei with ribosome-bound mRNA and MIRACL-seq for label-free enrichment of rare cell types by droplet-based profiling. The 1,187,535 nuclei in our mouse atlas include 5,068 neurons from the ileum and colon, revealing extraordinary neuron diversity. We highlight circadian expression changes in enteric neurons, show that disease-related genes are dysregulated with aging, and identify differences between the ileum and proximal/distal colon. In humans, we profile 436,202 nuclei, recovering 1,445 neurons, and identify conserved and species-specific transcriptional programs and putative neuro-epithelial, neuro-stromal, and neuro-immune interactions. The human ENS expresses risk genes for neuropathic, inflammatory, and extra-intestinal diseases, suggesting neuronal contributions to disease., Competing Interests: Declaration of Interests A.R. is a co-founder and equity holder of Celsius Therapeutics, equity holder of Immunitas, and, until August, 2020, an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov. A.R. is an employee of Genentech Inc. R.J.X. is a co-founder and equity holder of Celsius Therapeutics and Jnana Therapeutics. E.D. is an employee of Bristol-Myers Squibb. E.D., C.S., G.E., O.R.R., R.X., and A.R. are co-inventors on PCT/US2019/055894, which includes the methods of this manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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