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Reconstructing aspects of human embryogenesis with pluripotent stem cells.

Published version
Peer-reviewed

Type

Article

Change log

Abstract

Understanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind human embryogenesis remain largely unknown. Here, we attempt to model human early embryo development with expanded pluripotent stem cells (EPSCs) in 3-dimensions. We define a protocol that allows us to generate self-organizing cystic structures from human EPSCs that display some hallmarks of human early embryogenesis. These structures mimic polarization and cavitation characteristic of pre-implantation development leading to blastocyst morphology formation and the transition to post-implantation-like organization upon extended culture. Single-cell RNA sequencing of these structures reveals subsets of cells bearing some resemblance to epiblast, hypoblast and trophectoderm lineages. Nevertheless, significant divergences from natural blastocysts persist in some key markers, and signalling pathways point towards ways in which morphology and transcriptional-level cell identities may diverge in stem cell models of the embryo. Thus, this stem cell platform provides insights into the design of stem cell models of embryogenesis.

Description

Keywords

Pluripotent Stem Cells, Blastocyst, Humans, Adaptor Proteins, Signal Transducing, Cell Culture Techniques, Sequence Analysis, RNA, Gene Expression, Cell Lineage, Embryonic Development, Models, Biological, GATA3 Transcription Factor, Embryo, Mammalian, Phospholipase C beta, SOXB1 Transcription Factors, SOXF Transcription Factors, Single-Cell Analysis, Biomarkers

Journal Title

Nature communications

Conference Name

Journal ISSN

2041-1723

Volume Title

12

Publisher

Sponsorship
Wellcome Trust (098287/Z/12/Z)