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Series GSE84666 Query DataSets for GSE84666
Status Public on Nov 23, 2016
Title Engineered human pluripotent stem cell-derived intestinal tissues with a functional enteric nervous system
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The enteric nervous system (ENS) of the gastrointestinal (GI) tract controls many diverse functions including motility and epithelial permeability. Perturbations in ENS development or function are common, yet a human model to study ENS-intestinal biology is lacking. We have used a tissue engineering approach with pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining PSC-derived neural crest cells (NCCs) with developing human intestinal organoids (HIOs). When cultured alone, NCCs had full differentiation potential in vitro, however when recombined with HIOs they differentiated into neurons and glial cells. NCC-derived ENS neurons self-assembled within the developing intestinal mesenchyme and exhibited neuronal activity as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, formed interstitial cells of Cajal, and had an electro-mechanical coupling that regulated waves of propagating contraction. This is the first demonstration of a human PSC-derived intestinal tissue with a functional ENS.
Overall design We examined 4 conditions (3 replicates per condition) of HIO in vitro that include mRNA profiles of HIO (Control); HIO with NCCs (HIOs+ENS); HIO with PHOX2B-/+ NCCs (HIO+ENS_Phox2b_Het); HIO with PHOX2B-/- NCCs (HIO+ENS_Phox2b_Homo). Samples were sequenced using Illumina TruSeq RNA sample prep kit.
Contributor(s) Trisno S, Workman MM, Mahe MM, Wells JM
Citation(s) 27869805
NIH grant(s)
Grant ID Grant title Affiliation Name
U18 TR000546 Generating Human Intestinal Organoids with an ENS. CHILDREN'S HOSPITAL MEDICAL CENTER James M Wells
R01 DK092456 Human Endocrine Cell Development CHILDREN'S HOSPITAL MEDICAL CENTER NOAH Freeman SHROYER, James M Wells
U18 EB021780 Establishment of in vitro and in vivo models of human gastrointestinal organoids with a functional ENS CHILDREN'S HOSPITAL MEDICAL CENTER James M Wells, MICHAEL A. HELMRATH
U01 DK103117 Investigation of Regional Identity in Human Intestinal Stem Cells CHILDREN'S HOSPITAL MEDICAL CENTER NOAH Freeman SHROYER, James M Wells, MICHAEL A. HELMRATH
K99 DK110414 "Human in vivo model to study the role of a functional enteric nervous system on intestinal development and maturation" CHILDREN'S HOSPITAL MEDICAL CENTER Maxime Mickael Mahe
Submission date Jul 21, 2016
Last update date May 15, 2019
Contact name James M Wells
Organization name Cincinnati Children's Hospital Medical Center
Department Developmental Biology
Lab Wells Lab
Street address 3333 Burnet Avenue
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (12)
GSM2247360 HIO_1
GSM2247361 HIO_2
GSM2247362 HIO_3
BioProject PRJNA330789
SRA SRP079166

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84666_Normalized_Expression.xls.gz 4.6 Mb (ftp)(http) XLS
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Raw data are available in SRA
Processed data are available on Series record

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