The Human and Mouse Enteric Nervous System at Single-Cell Resolution.
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.
|Year of Publication||
2020 09 17
|PubMed Central ID||
P30 DK043351 / DK / NIDDK NIH HHS / United States
RC2 DK114784 / DK / NIDDK NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
K08 CA218420 / CA / NCI NIH HHS / United States
R01 DK117263 / DK / NIDDK NIH HHS / United States