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Blastocyst-like structures generated from human pluripotent stem cells.
Yu, Leqian; Wei, Yulei; Duan, Jialei; Schmitz, Daniel A; Sakurai, Masahiro; Wang, Lei; Wang, Kunhua; Zhao, Shuhua; Hon, Gary C; Wu, Jun.
Afiliação
  • Yu L; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Wei Y; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Duan J; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Schmitz DA; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.
  • Sakurai M; International Healthcare Innovation Institute, Jiangmen, China.
  • Wang L; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Wang K; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Zhao S; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Hon GC; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Wu J; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature ; 591(7851): 620-626, 2021 03.
Article em En | MEDLINE | ID: mdl-33731924
Limited access to embryos has hampered the study of human embryogenesis and disorders that occur during early pregnancy. Human pluripotent stem cells provide an alternative means to study human development in a dish1-7. Recent advances in partial embryo models derived from human pluripotent stem cells have enabled human development to be examined at early post-implantation stages8-14. However, models of the pre-implantation human blastocyst are lacking. Starting from naive human pluripotent stem cells, here we developed an effective three-dimensional culture strategy with successive lineage differentiation and self-organization to generate blastocyst-like structures in vitro. These structures-which we term 'human blastoids'-resemble human blastocysts in terms of their morphology, size, cell number, and composition and allocation of different cell lineages. Single-cell RNA-sequencing analyses also reveal the transcriptomic similarity of blastoids to blastocysts. Human blastoids are amenable to embryonic and extra-embryonic stem cell derivation and can further develop into peri-implantation embryo-like structures in vitro. Using chemical perturbations, we show that specific isozymes of protein kinase C have a critical function in the formation of the blastoid cavity. Human blastoids provide a readily accessible, scalable, versatile and perturbable alternative to blastocysts for studying early human development, understanding early pregnancy loss and gaining insights into early developmental defects.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Blastocisto / Diferenciação Celular / Células-Tronco Pluripotentes Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Blastocisto / Diferenciação Celular / Células-Tronco Pluripotentes Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos