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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Format: | Article |
Language: | English |
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Elsevier
2024-01-01
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Series: | iScience |
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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. |
first_indexed | 2024-03-08T19:01:51Z |
format | Article |
id | doaj.art-7a4a8a6eb06847588402732e66ef624f |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-03-08T19:01:51Z |
publishDate | 2024-01-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
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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