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Generation and molecular characterization of human pluripotent stem cell-derived pharyngeal foregut endoderm.
Kearns, Nicola A; Lobo, Macrina; Genga, Ryan M J; Abramowitz, Ryan G; Parsi, Krishna M; Min, Jiang; Kernfeld, Eric M; Huey, Jack D; Kady, Jamie; Hennessy, Erica; Brehm, Michael A; Ziller, Michael J; Maehr, René.
Afiliação
  • Kearns NA; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Lobo M; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Genga RMJ; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Abramowitz RG; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Parsi KM; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Min J; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Kernfeld EM; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Huey JD; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Kady J; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Hennessy E; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Brehm MA; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Ziller MJ; Department of Psychiatry, University of Münster, Münster, Germany.
  • Maehr R; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA; Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address: rene.maehr@umassmed.edu.
Dev Cell ; 58(18): 1801-1818.e15, 2023 09 25.
Article em En | MEDLINE | ID: mdl-37751684
ABSTRACT
Approaches to study human pharyngeal foregut endoderm-a developmental intermediate that is linked to various human syndromes involving pharynx development and organogenesis of tissues such as thymus, parathyroid, and thyroid-have been hampered by scarcity of tissue access and cellular models. We present an efficient stepwise differentiation method to generate human pharyngeal foregut endoderm from pluripotent stem cells. We determine dose and temporal requirements of signaling pathway engagement for optimized differentiation and characterize the differentiation products on cellular and integrated molecular level. We present a computational classification tool, "CellMatch," and transcriptomic classification of differentiation products on an integrated mouse scRNA-seq developmental roadmap confirms cellular maturation. Integrated transcriptomic and chromatin analyses infer differentiation stage-specific gene regulatory networks. Our work provides the method and integrated multiomic resource for the investigation of disease-relevant loci and gene regulatory networks and their role in developmental defects affecting the pharyngeal endoderm and its derivatives.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Faringe / Células-Tronco Pluripotentes Limite: Animals / Humans Idioma: En Revista: Dev Cell Assunto da revista: EMBRIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Faringe / Células-Tronco Pluripotentes Limite: Animals / Humans Idioma: En Revista: Dev Cell Assunto da revista: EMBRIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos