Carnegie in 4D? Stem-cell-based models of human embryo development

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

  • Berna Sozen - , Yale University (Author)
  • Deniz Conkar - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Jesse V. Veenvliet - , Max Planck Institute of Molecular Cell Biology and Genetics, TUD Dresden University of Technology, Clusters of Excellence PoL: Physics of Life (Author)

Abstract

How cells build embryos is still a major mystery. Many unresolved questions require the study of the processes that pattern and shape the embryo in live specimens, in toto, across spatial and temporal scales. In mammalian embryogenesis, this remains a major challenge as the embryo develops in utero, precluding easy accessibility. For human embryos, technical, ethical and legal limitations further hamper the in-depth investigation of embryogenesis, especially beyond gastrulation stages. This has resulted in an over-reliance on model organisms, particularly mice, to understand mammalian development. However, recent efforts show critical differences between rodent and primate embryos, including timing, architecture and transcriptional regulation. Thus, a human-centric understanding of embryogenesis is much needed. To empower this, novel in vitro approaches, which coax human pluripotent stem cells to form embryonic organoids that model embryo development, are pivotal. Here, we summarize these emergent technologies that recapitulate aspects of human development “in a dish”. We show how these technologies can provide insights into the molecular, cellular and morphogenetic processes that fuel the formation of a fully formed fetus, and discuss the potential of these platforms to revolutionize our understanding of human development in health and disease. Despite their clear promise, we caution against over-interpreting the extent to which these in vitro platforms model the natural embryo. In particular, we discuss how fate, form and function - a tightly coupled trinity in vivo, can be disconnected in vitro. Finally, we propose how careful benchmarking of existing models, in combination with rational protocol design based on an increased understanding of in vivo developmental dynamics and insights from mouse in vitro models of embryo development, will help guide the establishment of better models of human embryo development.

Details

Original languageEnglish
Pages (from-to)44-57
Number of pages14
JournalSeminars in Cell and Developmental Biology
Volume131
Publication statusPublished - Nov 2022
Peer-reviewedYes

External IDs

PubMed 35701286

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Embryogenesis, Embryoids, Embryonic organoids, Gastruloids, Human development, Stem cells

Library keywords