The Human and Mouse Enteric Nervous System at Single-Cell Resolution | Zendy

Eugene Drokhlyansky | Zendy; Christopher S. Smillie | Zendy; Nicholas Van Wittenberghe | Zendy; Maria Ericsson | Zendy; Gabriel K. Griffin | Zendy; Gökçen Eraslan | Zendy; Danielle Dionne | Zendy; Michael S. Cuoco | Zendy; Max N. Goder-Reiser | Zendy; Tatyana Sharova | Zendy; Olena Kuksenko | Zendy; Andrew J. Aguirre | Zendy; Genevieve M. Boland | Zendy; Daniel B. Graham | Zendy; Orit Rozenblatt–Rosen | Zendy; Ramnik J. Xavier | Zendy; Aviv Regev | Zendy

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The Human and Mouse Enteric Nervous System at Single-Cell Resolution

Author(s) -

Eugene Drokhlyansky,

Christopher S. Smillie,

Nicholas Van Wittenberghe,

Maria Ericsson,

Gabriel K. Griffin,

Gökçen Eraslan,

Danielle Dionne,

Michael S. Cuoco,

Max N. Goder-Reiser,

Tatyana Sharova,

Olena Kuksenko,

Andrew J. Aguirre,

Genevieve M. Boland,

Daniel B. Graham,

Orit Rozenblatt–Rosen,

Ramnik J. Xavier,

Aviv Regev

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.08.003

Subject(s) - biology , enteric nervous system , ileum , nervous system , cell type , microbiology and biotechnology , gene expression profiling , cell , stromal cell , single cell analysis , neuroscience , computational biology , gene , immunology , gene expression , genetics , cancer research , endocrinology

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.

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