Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma

Summary: Studies defining normal and disrupted human neural crest cell development have been challenging given its early timing and intricacy of development. Consequently, insight into the early disruptive events causing a neural crest related disease such as pediatric cancer neuroblastoma is limite...

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Main Authors: Stéphane Van Haver, Yujie Fan, Sarah-Lee Bekaert, Celine Everaert, Wouter Van Loocke, Vittorio Zanzani, Joke Deschildre, Inés Fernandez Maestre, Adrianna Amaro, Vanessa Vermeirssen, Katleen De Preter, Ting Zhou, Alex Kentsis, Lorenz Studer, Frank Speleman, Stephen S. Roberts
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223021739
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author Stéphane Van Haver
Yujie Fan
Sarah-Lee Bekaert
Celine Everaert
Wouter Van Loocke
Vittorio Zanzani
Joke Deschildre
Inés Fernandez Maestre
Adrianna Amaro
Vanessa Vermeirssen
Katleen De Preter
Ting Zhou
Alex Kentsis
Lorenz Studer
Frank Speleman
Stephen S. Roberts
author_facet Stéphane Van Haver
Yujie Fan
Sarah-Lee Bekaert
Celine Everaert
Wouter Van Loocke
Vittorio Zanzani
Joke Deschildre
Inés Fernandez Maestre
Adrianna Amaro
Vanessa Vermeirssen
Katleen De Preter
Ting Zhou
Alex Kentsis
Lorenz Studer
Frank Speleman
Stephen S. Roberts
author_sort Stéphane Van Haver
collection DOAJ
description Summary: Studies defining normal and disrupted human neural crest cell development have been challenging given its early timing and intricacy of development. Consequently, insight into the early disruptive events causing a neural crest related disease such as pediatric cancer neuroblastoma is limited. To overcome this problem, we developed an in vitro differentiation model to recapitulate the normal in vivo developmental process of the sympathoadrenal lineage which gives rise to neuroblastoma. We used human in vitro pluripotent stem cells and single-cell RNA sequencing to recapitulate the molecular events during sympathoadrenal development. We provide a detailed map of dynamically regulated transcriptomes during sympathoblast formation and illustrate the power of this model to study early events of the development of human neuroblastoma, identifying a distinct subpopulation of cell marked by SOX2 expression in developing sympathoblast obtained from patient derived iPSC cells harboring a germline activating mutation in the anaplastic lymphoma kinase (ALK) gene.
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spelling doaj.art-7a4a8a6eb06847588402732e66ef624f2023-12-28T05:18:35ZengElsevieriScience2589-00422024-01-01271108096Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastomaStéphane Van Haver0Yujie Fan1Sarah-Lee Bekaert2Celine Everaert3Wouter Van Loocke4Vittorio Zanzani5Joke Deschildre6Inés Fernandez Maestre7Adrianna Amaro8Vanessa Vermeirssen9Katleen De Preter10Ting Zhou11Alex Kentsis12Lorenz Studer13Frank Speleman14Stephen S. Roberts15Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, BelgiumThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA; Developmental Biology Program, MSKCC, New York, NY 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USADepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, BelgiumDepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, BelgiumDepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, BelgiumDepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Lab for Computational Biology, Integromics and Gene Regulation (CBIGR), Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, BelgiumDepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Lab for Computational Biology, Integromics and Gene Regulation (CBIGR), Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, BelgiumHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Louis V. Gerstner Jr Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pediatrics, MSKCC, New York, NY 10065, USADepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Lab for Computational Biology, Integromics and Gene Regulation (CBIGR), Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, BelgiumDepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, BelgiumThe SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USADepartment of Pediatrics, MSKCC, New York, NY 10065, USA; Molecular Pharmacology Program, MSKCC, New York, NY, USA; Tow Center for Developmental Oncology, MSKCC, New York, NY 10065, USA; Departments of Pediatrics, Pharmacology and Physiology & Biophysics, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USAThe Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA; Developmental Biology Program, MSKCC, New York, NY 10065, USADepartment of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, BelgiumDepartment of Pediatrics, MSKCC, New York, NY 10065, USA; Corresponding authorSummary: Studies defining normal and disrupted human neural crest cell development have been challenging given its early timing and intricacy of development. Consequently, insight into the early disruptive events causing a neural crest related disease such as pediatric cancer neuroblastoma is limited. To overcome this problem, we developed an in vitro differentiation model to recapitulate the normal in vivo developmental process of the sympathoadrenal lineage which gives rise to neuroblastoma. We used human in vitro pluripotent stem cells and single-cell RNA sequencing to recapitulate the molecular events during sympathoadrenal development. We provide a detailed map of dynamically regulated transcriptomes during sympathoblast formation and illustrate the power of this model to study early events of the development of human neuroblastoma, identifying a distinct subpopulation of cell marked by SOX2 expression in developing sympathoblast obtained from patient derived iPSC cells harboring a germline activating mutation in the anaplastic lymphoma kinase (ALK) gene.http://www.sciencedirect.com/science/article/pii/S2589004223021739CancerStem cells research
spellingShingle Stéphane Van Haver
Yujie Fan
Sarah-Lee Bekaert
Celine Everaert
Wouter Van Loocke
Vittorio Zanzani
Joke Deschildre
Inés Fernandez Maestre
Adrianna Amaro
Vanessa Vermeirssen
Katleen De Preter
Ting Zhou
Alex Kentsis
Lorenz Studer
Frank Speleman
Stephen S. Roberts
Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
iScience
Cancer
Stem cells research
title Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
title_full Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
title_fullStr Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
title_full_unstemmed Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
title_short Human iPSC modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
title_sort human ipsc modeling recapitulates in vivo sympathoadrenal development and reveals an aberrant developmental subpopulation in familial neuroblastoma
topic Cancer
Stem cells research
url http://www.sciencedirect.com/science/article/pii/S2589004223021739
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