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Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs

Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-cul...

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Autores principales: Langkabel, Jan, Horne, Arik, Bonaguro, Lorenzo, Holsten, Lisa, Hesse, Tatiana, Knaus, Alexej, Riedel, Yannick, Becker, Matthias, Händler, Kristian, Elmzzahi, Tarek, Bassler, Kevin, Reusch, Nico, Yeghiazarian, Leon Harootoonovtch, Pecht, Tal, Saglam, Adem, Ulas, Thomas, Aschenbrenner, Anna C., Kaiser, Franziska, Kubaczka, Caroline, Schultze, Joachim L., Schorle, Hubert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677818/
https://www.ncbi.nlm.nih.gov/pubmed/34916498
http://dx.doi.org/10.1038/s41467-021-27586-w
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author Langkabel, Jan
Horne, Arik
Bonaguro, Lorenzo
Holsten, Lisa
Hesse, Tatiana
Knaus, Alexej
Riedel, Yannick
Becker, Matthias
Händler, Kristian
Elmzzahi, Tarek
Bassler, Kevin
Reusch, Nico
Yeghiazarian, Leon Harootoonovtch
Pecht, Tal
Saglam, Adem
Ulas, Thomas
Aschenbrenner, Anna C.
Kaiser, Franziska
Kubaczka, Caroline
Schultze, Joachim L.
Schorle, Hubert
author_facet Langkabel, Jan
Horne, Arik
Bonaguro, Lorenzo
Holsten, Lisa
Hesse, Tatiana
Knaus, Alexej
Riedel, Yannick
Becker, Matthias
Händler, Kristian
Elmzzahi, Tarek
Bassler, Kevin
Reusch, Nico
Yeghiazarian, Leon Harootoonovtch
Pecht, Tal
Saglam, Adem
Ulas, Thomas
Aschenbrenner, Anna C.
Kaiser, Franziska
Kubaczka, Caroline
Schultze, Joachim L.
Schorle, Hubert
author_sort Langkabel, Jan
collection PubMed
description Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5–E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.
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spelling pubmed-86778182022-01-04 Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs Langkabel, Jan Horne, Arik Bonaguro, Lorenzo Holsten, Lisa Hesse, Tatiana Knaus, Alexej Riedel, Yannick Becker, Matthias Händler, Kristian Elmzzahi, Tarek Bassler, Kevin Reusch, Nico Yeghiazarian, Leon Harootoonovtch Pecht, Tal Saglam, Adem Ulas, Thomas Aschenbrenner, Anna C. Kaiser, Franziska Kubaczka, Caroline Schultze, Joachim L. Schorle, Hubert Nat Commun Article Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5–E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis. Nature Publishing Group UK 2021-12-16 /pmc/articles/PMC8677818/ /pubmed/34916498 http://dx.doi.org/10.1038/s41467-021-27586-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Langkabel, Jan
Horne, Arik
Bonaguro, Lorenzo
Holsten, Lisa
Hesse, Tatiana
Knaus, Alexej
Riedel, Yannick
Becker, Matthias
Händler, Kristian
Elmzzahi, Tarek
Bassler, Kevin
Reusch, Nico
Yeghiazarian, Leon Harootoonovtch
Pecht, Tal
Saglam, Adem
Ulas, Thomas
Aschenbrenner, Anna C.
Kaiser, Franziska
Kubaczka, Caroline
Schultze, Joachim L.
Schorle, Hubert
Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
title Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
title_full Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
title_fullStr Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
title_full_unstemmed Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
title_short Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
title_sort induction of rosette-to-lumen stage embryoids using reprogramming paradigms in escs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677818/
https://www.ncbi.nlm.nih.gov/pubmed/34916498
http://dx.doi.org/10.1038/s41467-021-27586-w
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