Human gastrulation: The embryo and its models

3D gastruloids: a novel frontier in stem cell-based in vitro modeling of mammalian gastrulation

“…Finally, work with human gastruloid models is associated with new ethical, societal, and regulatory questions [29,57,[67][68][69][70][71] that need to be addressed before the avenues described here can be pursued with human cells. While currently available versions of the human gastruloid model do not generate anterior neural or extraembryonic tissues and are therefore considered a safe alternative for human embryo research [24], it is not unlikely that more advanced versions of such models may appear in the future and it will not be straightforward to determine when these models become so advanced that their moral and regulatory status should be considered equivalent to that of the human embryo [69].…”

“…Given the rapid expansion of the gastruloid field, there is an increasing need for debates about the ethical aspects of human gastruloid models and for methods that improve the reproducibility of this emerging model system. cell-based embryo models that recapitulate earlier developmental stages, these models have several key advantages over mammalian embryos: they can be generated in large numbers, allowing screens; they are easier to genetically modify than embryos since they bypass the need to create genetically modified animals; they allow studies into stages of human development that are difficult to access for research; and their tractable nature allows experimental approaches that cannot readily be applied to embryos [26][27][28][29][30][31].…”

Biomedical and societal impacts of in vitro embryo models of mammalian development

“…The success rates of these experiments are still low, and routine practice of such approaches is still limited by the “special status” of human embryos ( Jones, 2011 ), for which some have argued that a 3Rs principle should also apply, similar to that used in animal research ( Bioethics, 2017 ). Notwithstanding these issues, recent experiments and emerging observations highlighting differences between mouse and human embryos ( Ghimire et al., 2021 ) have raised the need to modify the day-14 rule to be able to explore human development at peri-gastrulation stages ( Hurlbut et al., 2017 ; Hyun et al., 2016 ). In the meantime, the search for appropriate models to study this period of development has led to an increased use of closely related species, in particular non-human primates.…”

Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids

“…Early mammalian embryogenesis entails sequential specification of extraembryonic (ExE) and embryonic tissues, from which the three germ layers, ectoderm, mesoderm, and endoderm, arise and are shaped into the body plan during gastrulation ( Shahbazi and Zernicka-Goetz, 2018 ). The underlying cellular and molecular mechanisms have been extensively investigated in the mouse and, more recently, in nonhuman primates, in vitro cultured human embryos, and 2D or 3D human embryonic stem cell (hESC) models ( Ghimire et al., 2021 ).…”

“…Due to the ease of genetic manipulation and the ability to finely control experimental factors, in vitro stem cell systems have emerged as an invaluable tool for understanding the signaling cascades and transcriptional regulatory network underlying cell fate specification and morphogenesis during early human development ( Ghimire et al., 2021 ). These models include 2D micropatterned and 3D gastruloid ( Martyn et al, 2018 , 2019a ; Moris et al., 2020 ; Warmflash et al., 2014 ), and 3D early blastocyst ( Rivron et al., 2018 ) and pre-gastrulation EPI ( Simunovic et al., 2019 ) models.…”