Skip to main content

Currently Skimming:

5 Comparative Embryonic Development Across Species
Pages 75-98

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 75...
... However, rhesus macaque embryos and trophoblast stem cells may offer enhanced translatability for modeling human embryos. (Golos)
From page 76...
... (García-Castro) • It is possible to rapidly derive neural crest cells from human embryonic stem cells cultured in defined media and treated with Wnt, an approach that circumvents some of the chal lenges with accessing human embryos to study.
From page 77...
... Aneuploidy Frequency in Early Cleavage-Stage Embryos Across Mammals Chavez outlined what is known about the range of aneuploidy frequency at the early cleavage stage across different mammalian species. As previously stated, aneuploidy occurs in about 50–80 percent of human embryos and in around 74 percent of nonhuman primates, specifically rhesus macaque embryos (Daughtry et al., 2019)
From page 78...
... Defective spindle attachments involve some kind of non-attachment or abnormal attachment. Compromised cell cycle checkpoints suggest that abnormal events such as an anaphase lagging chromosome go unrecognized and that the embryo divides before it has a chance to line up on the spindle; this is an area in which much of the mouse embryo work has been done.
From page 79...
... Cellular fragmentation is distinct from the DNA fragmentation that can occur following cell death late in pre-implantation development and evidence suggests that it occurs in vivo for multiple species, including humans. Fragmented embryos often exhibit chromosome loss from blastomeres, Chavez said, which complicates aneuploidy assessment.
From page 80...
... However, because not every single embryo exhibited this phenotype, Chavez's group is investigating other mechanisms, such as chromatin or anaphase bridging. DNA Damage in Chromosome-Containing Cellular Fragments and Micronuclei Eighteen percent of the rhesus embryos in the study had chromosome-containing fragments, Chavez said, but only 6 percent of all the fragments had DNA detectable by sequencing.
From page 81...
... He described the formation of embryoid bodies from human embryonic stem cells and the use of rhesus embryoid bodies to model trophoblast differentiation. He also examined the predictive capacity of nonhuman primate embryo model systems.
From page 82...
... This work gave rise to the question of whether primate and human ESCs can provide a system for modeling trophoblast differentiation and placental morphogenesis. Spontaneous differentiation of hESCs to the trophoblast lineage in vitro or in teratomas is of low efficiency; a breakthrough occurred when Xu and colleagues discovered that bone morphogenetic protein 4 (BMP4)
From page 83...
... (2018) have reported the derivation of human trophoblast stem cells (TSCs)
From page 84...
... A strength of the nonhuman primate model, he said, is that it provides opportunities to interrogate through pre-implantation embryo manipulation different types of embryonic events that are critical for in vivo placentation, such as villous morphogenesis, spiral artery endovascular migration of EVT, and vessel remodeling. These are experiments that cannot be conducted at the requisite stage of human pregnancy, so toggling back and forth between different kinds of models may be needed in order to answer precise questions about the components that underlie pregnancy success and adverse pregnancy outcomes.
From page 85...
... They also contribute to cancers, including melanoma. Because neural crest cells are involved in so many pathologies, García-Castro said, these cells hold great promise for clinical studies.
From page 86...
... Ontogeny of Neural Crest García-Castro's laboratory is using a variety of model organisms and model systems to revisit the ontogeny of neural crest cells and determine when those cells are specified. Specification of Neural Crest Cell Fate The perception that neural processes are specified in the ectoderm comes from a series of studies from the 1980s and 1990s, which showed that neural crest cells appear in between the neural and non-neural ectoderm.
From page 87...
... After the explants had been incubated for a longer period, other neural crest markers emerged, and eventually the definitive markers of migratory neural crest cells were evident in the restricted intermediate territories. García-Castro and his colleagues followed up with a series of experiments to determine whether neural crest markers are induced in culture.
From page 88...
... . Modeling Early Human Neural Crest Development with Pluripotent Stem Cells Considering the question of whether human neural crest also specified before gastrulation and whether the knowledge gained from neural crest in chicks can be translated to humans, García-Castro said that knowledge of neural crest cell development in human embryos is still limited to histological descriptions of neural crest cells under migratory routes, with minimal molecular information available.
From page 89...
... Early Neural Crest Cell Development in Mammals Reflecting on how to translate gains from chick and model human neural crest studies to mammalian embryos in order to enable more robust comparisons, García-Castro said that much progress has been made using mouse models to study neural crest cells in the later stages of development, but little is known about how the neural crest cells are formed or specified (Murdoch et al., 2010, 2012)
From page 90...
... Over time, they express crest markers, and they are subjected to signaling restrictions similar to those found in the chick. BLASTOCYST-LIKE STRUCTURES GENERATED FROM PLURIPOTENT STEM CELLS WITH EXPANDED POTENTIAL Jun Wu, an assistant professor of molecular biology at the University of Texas Southwestern Medical Center, explained how blastocyst-like structures (blastoids)
From page 91...
... In order to generate a blastocyst-like structure, the naïve pluripotent stem cell would seem to be the logical choice, Wu said; however, the b ­ lastocyst contains more than one cell type, so generating a blastocyst ­ requires at least two to three different types of cells. Over the past several decades, three stem cell lines have been generated: trophoblast stem cells (TSCs)
From page 92...
... 92 FIGURE 5-1  Blastocyst-like structure generated in vitro using expanded- or extended-potential stem cells. NOTE: EPS = expanded-potential stem; ESC = embryonic stem cell; TSC = trophoblast stem cell; XEN = extraembryonic endoderm.
From page 93...
... Second Cell Fate Determination in EPS-Blastoids: Epiblast and Primitive Endoderm Next, Wu and colleagues looked at whether EPS-blastoids could further develop into structures resembling a mature blastocyst, which contains three cell lineages instead of two. In some of the EPS-blastoids, they observed that some inside cells expressed GATA4, a marker of the primitive endoderm (PE)
From page 94...
... He and his colleagues observed that in about 80 percent of the structures, the TE-like layer preferentially silenced the X chromosome from the paternal side. A functional test of the EPS-blastoid was whether it could be used to derive all three types of stem cells, Wu said.
From page 95...
... PANEL DISCUSSION Use of Human Expanded-Potential Stem Cells in Mouse Models Why do hEPSCs not appear to work as well as mouse EPSCs in the model produced by Wu's team? one workshop participant asked.
From page 96...
... Although there are pockets of in situ trophoblasts, they do not intrude substantially into the decidua, as the human embryo does. This suggests that nonhuman primates may not provide the best model for understanding the earliest events contributing to the high rate of implantation failure in human embryos, he said.
From page 97...
... However, comparing transcriptomes from pluripotent stem cells cultured in vitro to in vivo embryos shows that in vitro cultured cells always cluster together and separate from in vivo counterparts, regardless of the culture conditions used. This suggests that there are some in vivo features that have not yet
From page 98...
... other features differ between in vivo and in vitro, such as metabolic and epigenetic features. Chavez added that an ongoing metabolomics analysis of monkey oocytes fertilized in culture from which the spent culture media was obtained indicates that stress may actually be set up even in the oocyte.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.