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Cardioids reveal self-organizing principles of human cardiogenesis.
Hofbauer, Pablo; Jahnel, Stefan M; Papai, Nora; Giesshammer, Magdalena; Deyett, Alison; Schmidt, Clara; Penc, Mirjam; Tavernini, Katherina; Grdseloff, Nastasja; Meledeth, Christy; Ginistrelli, Lavinia Ceci; Ctortecka, Claudia; Salic, Sejla; Novatchkova, Maria; Mendjan, Sasha.
Afiliação
  • Hofbauer P; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Jahnel SM; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Papai N; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Giesshammer M; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Deyett A; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Schmidt C; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Penc M; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Tavernini K; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Grdseloff N; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Meledeth C; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Ginistrelli LC; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Ctortecka C; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Salic S; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria.
  • Novatchkova M; Institute of Molecular Pathology (IMP), Vienna Biocenter 1, 1030 Vienna, Austria.
  • Mendjan S; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, Dr. Bohr Gasse 3, 1030 Vienna, Austria. Electronic address: sasha.mendjan@imba.oeaw.ac.at.
Cell ; 184(12): 3299-3317.e22, 2021 06 10.
Article em En | MEDLINE | ID: mdl-34019794
Organoids capable of forming tissue-like structures have transformed our ability to model human development and disease. With the notable exception of the human heart, lineage-specific self-organizing organoids have been reported for all major organs. Here, we established self-organizing cardioids from human pluripotent stem cells that intrinsically specify, pattern, and morph into chamber-like structures containing a cavity. Cardioid complexity can be controlled by signaling that instructs the separation of cardiomyocyte and endothelial layers and by directing epicardial spreading, inward migration, and differentiation. We find that cavity morphogenesis is governed by a mesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factor linked to developmental heart chamber defects. Upon cryoinjury, cardioids initiated a cell-type-dependent accumulation of extracellular matrix, an early hallmark of both regeneration and heart disease. Thus, human cardioids represent a powerful platform to mechanistically dissect self-organization, congenital heart defects and serve as a foundation for future translational research.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Organoides / Organogênese / Coração Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Áustria

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Organoides / Organogênese / Coração Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Áustria