Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease.
human fetal gut development
inflammatory bowel disease
intestinal organoids
intestinal stem cells
pediatric Crohn's disease
single-cell RNA sequencing
villus formation
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
21 12 2020
21 12 2020
Historique:
received:
30
04
2020
revised:
04
09
2020
accepted:
06
11
2020
pubmed:
9
12
2020
medline:
16
3
2021
entrez:
8
12
2020
Statut:
ppublish
Résumé
Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map of the developing human intestine at 6-10 weeks post-conception. Our analysis reveals the transcriptional profile of cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated cell subsets via the generation of LGR5-expressing stem cells and receive signals from surrounding mesenchymal cells. Furthermore, we draw parallels between the transcriptomes of ex vivo tissues and in vitro fetal organoids, revealing the maturation of organoid cultures in a dish. Lastly, we compare scRNA-seq profiles from pediatric Crohn's disease epithelium alongside matched healthy controls to reveal disease-associated changes in the epithelial composition. Contrasting these with the fetal profiles reveals the re-activation of fetal transcription factors in Crohn's disease. Our study provides a resource available at www.gutcellatlas.org, and underscores the importance of unraveling fetal development in understanding disease.
Identifiants
pubmed: 33290721
pii: S1534-5807(20)30886-8
doi: 10.1016/j.devcel.2020.11.010
pmc: PMC7762816
pii:
doi:
Substances chimiques
LGR5 protein, human
0
Receptors, G-Protein-Coupled
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
771-783.e5Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/N001540/1
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/T2T0419
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701448
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T001917/1
Pays : United Kingdom
Organisme : European Research Council
ID : 646794
Pays : International
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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