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Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm.
Cipriano, Andrea; Colantoni, Alessio; Calicchio, Alessandro; Fiorentino, Jonathan; Gomes, Danielle; Moqri, Mahdi; Parker, Alexander; Rasouli, Sajede; Caldwell, Matthew; Briganti, Francesca; Roncarolo, Maria Grazia; Baldini, Antonio; Weinacht, Katja G; Tartaglia, Gian Gaetano; Sebastiano, Vittorio.
Afiliación
  • Cipriano A; Department of Obstetrics & Gynecology, Stanford University, Stanford, CA, 94305, USA.
  • Colantoni A; Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Calicchio A; Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, 00185, Rome, Italy.
  • Fiorentino J; Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano Di Tecnologia (IIT), 00161, Rome, Italy.
  • Gomes D; Department of Obstetrics & Gynecology, Stanford University, Stanford, CA, 94305, USA.
  • Moqri M; Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Parker A; Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano Di Tecnologia (IIT), 00161, Rome, Italy.
  • Rasouli S; Department of Obstetrics & Gynecology, Stanford University, Stanford, CA, 94305, USA.
  • Caldwell M; Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Briganti F; Biomedical Informatics Program, Department of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA.
  • Roncarolo MG; Department of Obstetrics & Gynecology, Stanford University, Stanford, CA, 94305, USA.
  • Baldini A; Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Weinacht KG; Department of Obstetrics & Gynecology, Stanford University, Stanford, CA, 94305, USA.
  • Tartaglia GG; Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford School of Medicine, Stanford, CA, 94305, USA.
  • Sebastiano V; Department of Obstetrics & Gynecology, Stanford University, Stanford, CA, 94305, USA.
Genome Biol ; 25(1): 211, 2024 Aug 08.
Article en En | MEDLINE | ID: mdl-39118163
ABSTRACT

BACKGROUND:

The Pharyngeal Endoderm (PE) is an extremely relevant developmental tissue, serving as the progenitor for the esophagus, parathyroids, thyroids, lungs, and thymus. While several studies have highlighted the importance of PE cells, a detailed transcriptional and epigenetic characterization of this important developmental stage is still missing, especially in humans, due to technical and ethical constraints pertaining to its early formation.

RESULTS:

Here we fill this knowledge gap by developing an in vitro protocol for the derivation of PE-like cells from human Embryonic Stem Cells (hESCs) and by providing an integrated multi-omics characterization. Our PE-like cells robustly express PE markers and are transcriptionally homogenous and similar to in vivo mouse PE cells. In addition, we define their epigenetic landscape and dynamic changes in response to Retinoic Acid by combining ATAC-Seq and ChIP-Seq of histone modifications. The integration of multiple high-throughput datasets leads to the identification of new putative regulatory regions and to the inference of a Retinoic Acid-centered transcription factor network orchestrating the development of PE-like cells.

CONCLUSIONS:

By combining hESCs differentiation with computational genomics, our work reveals the epigenetic dynamics that occur during human PE differentiation, providing a solid resource and foundation for research focused on the development of PE derivatives and the modeling of their developmental defects in genetic syndromes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Epigénesis Genética / Endodermo / Células Madre Embrionarias Humanas Límite: Animals / Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Epigénesis Genética / Endodermo / Células Madre Embrionarias Humanas Límite: Animals / Humans Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido