ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/009/SRR5605739/SRR5605739_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/008/SRR5605738/SRR5605738_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/006/SRR5605736/SRR5605736_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/009/SRR5605739/SRR5605739_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/005/SRR5605735/SRR5605735_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/006/SRR5605736/SRR5605736_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/007/SRR5605737/SRR5605737_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/004/SRR5605734/SRR5605734_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/008/SRR5605738/SRR5605738_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/005/SRR5605735/SRR5605735_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/004/SRR5605734/SRR5605734_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR560/007/SRR5605737/SRR5605737_1.fastq.gzprimaryOK200GenomicsGrubbs, Obstetrics and Gynecology, University of Southern Californiahttps://www.ebi.ac.uk/ena/browser/view/PRJNA388097Homo sapiensxref:PubMed:28803915Acquired or congenital disruption in enteric nervous system (ENS) development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC)-derived tissue-engineered small intestine (TESI) from human intestinal organoids (HIO). However, HIO-TESI fails to develop an ENS. In a previous report of combined HIO with additional human enteric neural crest cells (ENCC), an ENS was established but lacked maturity. The purpose of our study is to establish a mature ENS derived exclusively from hPSC in HIO-TESI. hPSC-derived ENCC supplementation of HIO-TESI generates ENCC-HIO-TESI with mature submucosal and myenteric ganglia, repopulates excitatory, inhibitory, and sensory neurons, and restores the neuroepithelial circuit and neuron-dependent contractility and relaxation. Our findings validate a novel approach to restoring a functional hPSC-derived ENS in ENCC-HIO-TESI and implicate their potential for the treatment of enteric neuropathies. Overall design: Examination of HIO-TESI growth with and without the addition of HESC-derived ENCC.ENAfalseHomo sapiensMaturing an Enteric Nervous System in Human Intestinal Organoid-derived Tissue-Engineered Small Intestine2025-09-242017-10-23PRJNA388097GSE99317960628803915