All models are wrong, but some are useful: Establishing standards for stem cell-based embryo models

Abstract

Detailed studies of the embryo allow an increasingly mechanistic understanding of development, which has proved of profound relevance to human disease. The last decade has seen in vitro cultured stem cell-based models of embryo development flourish, which provide an alternative to the embryo for accessible experimentation. However, the usefulness of any stem cell-based embryo model will be determined by how accurately it reflects in vivo embryonic development, and/or the extent to which it facilitates new discoveries. Stringent benchmarking of embryo models is thus an important consideration for this growing field. Here we provide an overview of means to evaluate both the properties of stem cells, the building blocks of most embryo models, as well as the usefulness of current and future in vitro embryo models.

Keywords: embryo models; in vitro; stem cells.

Figure 1

Timeline of embryonic development in mouse and human Key cell types are shown across embryonic days (E) for the mouse, while for the corresponding Carnegie stage is shown for humans. Bottom panel shows a summary of the models of embryonic development (see Table 2), the corresponding embryonic stage they model, and species in which they have been developed so far. Abbreviations: PE, primitive endoderm (hypoblast); TE, trophectoderm; EPI, epiblast; ExE, extraembryonic ectoderm; CS, Carnegie stage.

Figure 2

Ways to evaluate stem cells, illustrated by properties of mESCs Single-cell UMAP based on data from (Posfai et al., 2021); epigenetic characteristics from (Buecker et al., 2014); remaining elements are unpublished data provided by the authors.