Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease

ABSTRACT: In this study, we performed single-cell transcriptional profiling of human embryonic and fetal gut samples obtained from 9 human embryos spanning ages 6-10 PCW and three regions (duo-jejunum, ileum and colon). Additionally, we profile mucosal biopsies from the terminal ileum of healthy children aged 4-12 years (n = 8) as well as a group of children newly diagnosed with Crohn’s disease (CD) (n = 7), a common form of IBD. Tissue samples were treated using an enzymatic dissociation protocol and single cell suspensions were then processed using the 3’v2 10x Genomics Chromium workflow. In a subset of samples, the intestinal epithelial cell fraction was enriched by performing magnetic bead sorting for EPCAM. In total, we generate single cell transcriptomes of ~90,000 primary human intestinal cells providing a rich resource and detailed roadmap. Using this data as well as scRNAseq profiles of human fetal gut derived organoids we describe embryonic and fetal epithelium composition, trace their differentiation dynamics and signaling partners, and provide links to regenerating Crohn’s disease epithelium.

INSTRUMENT(S): MACS, Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Heuschkel 

PROVIDER: E-MTAB-8901 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress