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In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
Published on: March 16, 2017
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Pluripotent state transitions coordinate morphogenesis in mouse and human embryos
Marta N Shahbazi1, Antonio Scialdone2, Natalia Skorupska1
1Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB2 3EG, UK.
Nature
|November 30, 2017
Summary
Exit from naive pluripotency is crucial for mammalian embryo development. This transition enables epiblast epithelialization and the formation of essential cavities, like the pro-amniotic cavity in mice and amniotic cavity in humans.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Cellular Biology
Background:
- Mammalian development originates from epiblast stem cells undergoing epithelialization.
- Pluripotent states are molecularly characterized but their developmental roles are unclear.
- Epithelialization and cavity formation are fundamental early developmental events.
Purpose of the Study:
- To investigate the biological significance of pluripotent states during mammalian embryonic development.
- To determine the role of exiting the naive pluripotent state in epiblast epithelialization and cavity formation.
- To elucidate the molecular mechanisms linking pluripotency exit to lumenogenesis.
Main Methods:
- Utilized mouse embryos and cultured human post-implantation embryos.
- Employed embryonic stem cells to model naive pluripotency.
- Analyzed gene expression, protein localization, and tissue morphology.
Main Results:
- Exit from naive pluripotency is essential for epiblast epithelialization and pro-amniotic cavity formation in mouse embryos.
- Embryonic stem cells in the naive state can polarize but fail to form lumens.
- Exit from naive pluripotency activates an Oct4-dependent transcriptional program, leading to sialomucin expression and lumenogenesis.
- In human embryos, exiting naive pluripotency triggers amniotic cavity formation and development.
Conclusions:
- Transitions between pluripotent states are critical for establishing tissue architecture during mammalian development.
- Pluripotency exit is a prerequisite for lumenogenesis and developmental progression.
- Tissue-level architecture provides a new criterion for defining pluripotent states.
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