ArticleCell stem cell2023
hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease.
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Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
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31 citing papers in PubMed.
- Functional maturation of enteric neurons derived from human induced pluripotent stem cells.Stem cell reports · 2026Article
- Total colonic aganglionosis: a bibliometric analysis of trends and themes (1978-2024).Orphanet journal of rare diseases · 2026Article
- Modelling co-development between the somites and neural tube in human trunk-like structures.Nature cell biology · 2025Article
- Article
- Dual SMAD inhibition as a versatile platform in human pluripotent stem cell-based regenerative medicine and disease modeling.Molecules and cells · 2025Review
- hPSC-derived sacral neural crest cells restore erectile function in pelvic ganglia injury.Stem cell research & therapy · 2025Article
- Article
- Scientific evolution from the definition of Hirschsprung disease to the present: a bibliometric analysis (1980-2023).Pediatric research · 2025Article
- Leveraging CRISPR activation for rapid assessment of gene editing products in human pluripotent stem cells.Stem cell reports · 2025Article
- Current and future state of the management of Hirschsprung disease.World journal of pediatric surgery · 2025Review
- Enhancing Retinal Regeneration through Dental Pulp Stem Cells -Based 3D Organoid Culture, Cytokine Regulation and Gene Editing Technologies.Stem cell reviews and reports · 2024Article
- Article
- Advances in human pluripotent stem cell reporter systems.iScience · 2024Review
- Human cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder.Nature communications · 2024Article
- Bioengineering of Intestinal Grafts.Gastroenterology clinics of North America · 2024Review
- Article
- GFRA4 is a new piece of the enteric neuronal system.Pediatric research · 2024Article
- Enteric neural stem cell transplant restores gut motility in mice with Hirschsprung disease.JCI insight · 2024Article
- Generation of human cerebral organoids with a structured outer subventricular zone.Cell reports · 2024Article
- Review
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Authors and funding
21 authors.
Yujie FanThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA.
James HacklandThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Arianna BaggioliniThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Lin Y HungDepartment of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA.
Huiyong ZhaoAntitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Paul ZumboDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA; Applied Bioinformatics Core, Weill Cornell Medicine, New York, NY 10065, USA.
Polina OberstThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Andrew P MinottiThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA.
Emiliano HergenrederThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA.
Sarah NajjarDepartment of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA.
Zixing HuangDepartment of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA.
Nelly M CruzCancer Biology and Genetics and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Aaron ZhongThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mega SidhartaThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ting ZhouThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elisa de StanchinaAntitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Doron BetelApplied Bioinformatics Core, Weill Cornell Medicine, New York, NY 10065, USA; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Richard M WhiteCancer Biology and Genetics and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Michael GershonDepartment of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Kara Gross MargolisDepartment of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA; Department of Pediatrics, NYU Grossman School of Medicine, New York, NY 10010, USA.
Lorenz StuderThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: studerl@mskcc.org.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MMICROENVIRONMENT IN ENTERIC NEURON DEVELOPMENTR01NS015547 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GERSHON, MICHAEL D, MARGOLIS, KARA GROSS · 1985 to 2022
$7.2MMODELING ENTERIC NERVOUS SYSTEM DEVELOPMENT AND HIRSCHSPRUNG'S DISASE IN HUMAN PLURIPOTENT STEM CELLSR01NS099270 · NINDS · SLOAN-KETTERING INST CAN RESEARCH · PI STUDER, LORENZ P. · 2016 to 2020
$2.9MA Prospective Study Examining the Role of Gestational SSRI Exposure in the Development of Functional Gastrointestinal DisordersR01DK130517 · NIDDK · NEW YORK UNIVERSITY · PI MARGOLIS, KARA GROSS, SAVIDGE, TOR C. · 2021 to 2024
$2.5MLinkage of s100a10 (p11) to enteric 5-HT4-mediated serotonergic signaling roles in GI motility, enteric nervous system development, and co-morbid dysfunction of gut and brainR01DK126644 · NIDDK · NEW YORK UNIVERSITY · PI MARGOLIS, KARA GROSS · 2021 to 2024
$1.9MThe role of mucosal serotonin in visceral nociception and gut motilityF32DK132810 · NIDDK · NEW YORK UNIVERSITY · PI NAJJAR, SARAH · 2022 to 2024
$218kLoss of nuclear integrity is sufficient to induce age-associated changes and Alzheimer's pathology in hPSC-derived cortical neurons.F31AG067709 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI MINOTTI, ANDREW · 2020 to 2022
$138kNCI NIH HHS P30 CA008748NIA NIH HHS F31 AG067709NIDDK NIH HHS F32 DK132810NIDDK NIH HHS R01 DK126644NIDDK NIH HHS R01 DK130517NINDS NIH HHS R01 NS015547NINDS NIH HHS R01 NS099270
Abstract
The enteric nervous system (ENS) is derived from both the vagal and sacral component of the neural crest (NC). Here, we present the derivation of sacral ENS precursors from human PSCs via timed exposure to FGF, WNT, and GDF11, which enables posterior patterning and transition from posterior trunk to sacral NC identity, respectively. Using a SOX2::H2B-tdTomato/T::H2B-GFP dual reporter hPSC line, we demonstrate that both trunk and sacral NC emerge from a double-positive neuro-mesodermal progenitor (NMP). Vagal and sacral NC precursors yield distinct neuronal subtypes and migratory behaviors in vitro and in vivo. Remarkably, xenografting of both vagal and sacral NC lineages is required to rescue a mouse model of total aganglionosis, suggesting opportunities in the treatment of severe forms of Hirschsprung's disease.
Indexed as
Hirschsprung DiseaseAnimalsBone Morphogenetic ProteinsDisease Models, AnimalGrowth Differentiation FactorsHeterograftsHistonesHumansMiceNeural CrestBone Morphogenetic ProteinsGDF11 protein, humanGrowth Differentiation FactorsHistonesaxial patterningaxial progenitorscell therapydirected differentiationenteric nervous systemGDF11Hirschsprung's diseasenervous system disorderneural crest developmentpluripotent stem cellsregenerative medicinesacral neural crest
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