PT  - JOURNAL ARTICLE
AU  - Eugene Drokhlyansky
AU  - Christopher S. Smillie
AU  - Nicholas Van Wittenberghe
AU  - Maria Ericsson
AU  - Gabriel K. Griffin
AU  - Danielle Dionne
AU  - Michael S. Cuoco
AU  - Max N. Goder-Reiser
AU  - Tatyana Sharova
AU  - Andrew J. Aguirre
AU  - Genevieve M. Boland
AU  - Daniel Graham
AU  - Orit Rozenblatt-Rosen
AU  - Ramnik J. Xavier
AU  - Aviv Regev
TI  - The enteric nervous system of the human and mouse colon at a single-cell resolution
AID  - 10.1101/746743
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 746743
4099  - http://biorxiv.org/content/early/2019/08/30/746743.short
4100  - http://biorxiv.org/content/early/2019/08/30/746743.full
AB  - As the largest branch of the autonomic nervous system, the enteric nervous system (ENS) controls the entire gastrointestinal tract, but remains incompletely characterized. Here, we develop RAISIN RNA-seq, which enables the capture of intact single nuclei along with ribosome-bound mRNA, and use it to profile the adult mouse and human colon to generate a reference map of the ENS at a single-cell resolution. This map reveals an extraordinary diversity of neuron subsets across intestinal locations, ages, and circadian phases, with conserved transcriptional programs that are shared between human and mouse. These data suggest possible revisions to the current model of peristalsis and molecular mechanisms that may allow enteric neurons to orchestrate tissue homeostasis, including immune regulation and stem cell maintenance. Human enteric neurons specifically express risk genes for neuropathic, inflammatory, and extra-intestinal diseases with concomitant gut dysmotility. Our study therefore provides a roadmap to understanding the ENS in health and disease.