Table 1. Comparison of published stem cell-based models of the post-implantation human embryo.

	Zheng et al.176	Weatherbee et al.10	Pedroza et al.11	Ai et al.111	Oldak et al.12	Hislop et al.188	Liu et al.181	Okubo et al.71
Starting cell types	primed human PSCs	intermediate human PSCs that are differentiated to epiblast-like, hypoblast-like, and trophoblast-like cells via transgene overexpression	intermediate human PSCs	naive human PSCs and extra-embryonic-like stem cells	naive human PSCs that are differentiated to hypoblast-like, ExM-like, and trophoblast-like cells and combined with naive human PSCs	primed human PSCs combined with yolk sac-like cells generated via transgene overexpression	extended potential human PSCs	naive human PSCs combined with hypoblast-like generated via transgene overexpression
Forced expression of transgene	no	yes	no	no	no	yes	no	yes
Experimental approach	growth in a 3D gel of defined physical properties coupled to a microfluidics device	aggregation and self-organization in suspension	aggregation and self-organization in suspension	aggregation and self-assembly in suspension	aggregation and self-assembly in suspension	self-assembly on 2D culture plates	aggregation and self-organization in suspension	aggregation and self-assembly in suspension
Stage modeled	early gastrulation	early post-implantation	early post-implantation	early post-implantation	early post-implantation	post-gastrulation development of extra-embryonic tissues	gastrulation	early post-implantation
Advantages	robust and reproducible	modularity	easy to set up	modularity and methodology informed by embryonic signaling	modularity and high morphological resemblance to day 12–14 post-implantation embryos	modular and easy to set up	advanced developmental stages reached and easy to set up	modular and easy to set up
Limitations
Implementation	requires microfluidics expertise	differences in the expression levels of the exogenous transcription factors may lead to differences in outcome	N/A	involves several cell types and differentiation protocols	involves several cell types and differentiation protocols	differences in the expression levels of the exogenous transcription factor may lead to differences in outcome	N/A	N/A
Embryonic tissue	N/A	excessive differentiation leading to loss of pluripotent cells and excessive ExM cells	limited post-implantation morphogenesis	N/A	N/A	the epiblast-like domain is developing on 2D plastic	derived from expanded potential stem cells, which have an unclear pluripotent state	N/A
Extra-embryonic tissues	not present	lack of bona fide trophoblast and visceral endoderm cells do not form a yolk sac	no ExM, no trophoblast, and the visceral endoderm does not form a yolk sac	extra-embryonic cell types without an in vivo counterpart	incomplete development of the trophoblast	no trophoblast	no trophoblast	trophoblast cells are not in direct physical contact with the epiblast, and visceral endoderm cells do not form a yolk sac
Efficiency	high	intermediate	intermediate	intermediate	low	high	intermediate	intermediate
Suitability for studies
Study of cell fate decisions and tissue crosstalk	yes	yes	yes	yes	yes	yes	yes	yes
Study of tissue morphogenesis	limited to epiblast and amnion	limited to epiblast and amnion	limited to epiblast and amnion	limited to epiblast, amnion, and yolk sac	limited to epiblast, amnion, and yolk sac	limited to epiblast, amnion, and yolk sac	limited to epiblast, amnion, and yolk sac	limited to epiblast and amnion
High-throughput studies	yes	no	no	no	no	yes	no	no
Labeling individual starting cell types to dissect tissue of origin	no	yes	no	yes	yes	yes	no	yes