[
{
"id": "authors:v27bb-hhe02",
"collection": "authors",
"collection_id": "v27bb-hhe02",
"cite_using_url": "https://authors.library.caltech.edu/records/v27bb-hhe02",
"type": "article",
"title": "Efficient stem cell-derived mouse embryo models for environmental studies",
"author": [
{
"family_name": "Jorgensen",
"given_name": "Victoria",
"orcid": "0000-0002-4205-6198",
"clpid": "Jorgensen-Victoria-Lynn"
},
{
"family_name": "Bao",
"given_name": "Min",
"orcid": "0009-0002-4247-3511",
"clpid": "Bao-Min"
},
{
"family_name": "Junyent",
"given_name": "Sergi",
"orcid": "0000-0003-2405-5885",
"clpid": "Junyent-Sergi"
},
{
"family_name": "H\u00e4felfinger",
"given_name": "Christoph M.",
"orcid": "0009-0000-2800-9144",
"clpid": "H\u00e4felfinger-Christoph-M"
},
{
"family_name": "Amaya",
"given_name": "Laura",
"orcid": "0000-0002-8742-9111",
"clpid": "Amaya-Laura"
},
{
"family_name": "Liao",
"given_name": "Zhaodi",
"orcid": "0000-0002-5387-732X",
"clpid": "Liao-Zhaodi"
},
{
"family_name": "Williams",
"given_name": "Brian A.",
"orcid": "0000-0003-3253-611X",
"clpid": "Williams-Brian-A"
},
{
"family_name": "Chen",
"given_name": "Dong-Yuan",
"orcid": "0000-0003-2179-2847",
"clpid": "Chen-Dong-Yuan"
},
{
"family_name": "Wu",
"given_name": "Amanda",
"orcid": "0000-0001-9546-1472"
},
{
"family_name": "Thomson",
"given_name": "Matt",
"orcid": "0000-0003-1021-1234",
"clpid": "Thomson-M-W"
},
{
"family_name": "Zernicka-Goetz",
"given_name": "Magdalena",
"orcid": "0000-0002-7004-2471",
"clpid": "Zernicka-Goetz-M"
}
],
"abstract": "Blastoids are stem cell-derived structures that mimic natural blastocysts by incorporating all three lineages: trophectoderm, epiblast, and primitive endoderm. However, current methods often yield incomplete structures that fail to cavitate or to form a proper primitive endoderm. To overcome these limitations, we develop a modular approach by aggregating three murine stem cell types: embryonic stem cells (ESCs), ESCs with inducible GATA4 expression (iG4-ESCs), and trophoblast stem cells (TSCs). This method yields cavitated blastocyst-like structures-termed iG4-blastoids-with approximately 80% efficiency. Single-cell RNA sequencing confirms their close resemblance to mature mouse blastocysts. Notably, culturing iG4-blastoids without FGF4 enhances specification of the invasive mural trophectoderm, and approximately 12% of structures undergo post-implantation-like morphogenesis in vitro. Using this model, we show that caffeine, alcohol, nicotine, and amino acid variations affect iG4-blastoids and natural embryos similarly, underscoring their utility as a robust model for investigating the impact of diverse environmental factors on embryogenesis.",
"doi": "10.1016/j.devcel.2025.08.004",
"issn": "1534-5807",
"publisher": "Elsevier",
"publication": "Developmental Cell",
"publication_date": "2026-01-14",
"series_number": "1",
"volume": "61",
"issue": "1",
"pages": "193-207.e6"
},
{
"id": "authors:mb1xy-59651",
"collection": "authors",
"collection_id": "mb1xy-59651",
"cite_using_url": "https://authors.library.caltech.edu/records/mb1xy-59651",
"type": "article",
"title": "Fertilization triggers early proteomic symmetry breaking in mammalian embryos",
"author": [
{
"family_name": "Iwamoto-Stohl",
"given_name": "Lisa K.",
"orcid": "0000-0003-0776-054X",
"clpid": "Iwamoto-Stohl-Lisa-K"
},
{
"family_name": "Petelski",
"given_name": "Aleksandra A."
},
{
"family_name": "Quan",
"given_name": "Baiyi",
"orcid": "0000-0001-6313-4274",
"clpid": "Quan-Baiyi"
},
{
"family_name": "Meglicki",
"given_name": "Maciej"
},
{
"family_name": "Fu",
"given_name": "Audrey"
},
{
"family_name": "Nakagawa",
"given_name": "Shoma",
"orcid": "0000-0002-7766-613X",
"clpid": "Nakagawa-Shoma"
},
{
"family_name": "McMahon",
"given_name": "Breanna",
"orcid": "0009-0001-3618-9664",
"clpid": "McMahon-Breanna-M"
},
{
"family_name": "Wang",
"given_name": "Ting-Yu",
"orcid": "0000-0002-9014-6825",
"clpid": "Wang-Ting-Yu"
},
{
"family_name": "Khan",
"given_name": "Saad"
},
{
"family_name": "Specht",
"given_name": "Harrison"
},
{
"family_name": "Huffman",
"given_name": "Gray"
},
{
"family_name": "Derks",
"given_name": "Jason"
},
{
"family_name": "Junyent",
"given_name": "Sergi",
"orcid": "0000-0003-2405-5885",
"clpid": "Junyent-Sergi"
},
{
"family_name": "Weatherbee",
"given_name": "Bailey A.T."
},
{
"family_name": "Weberling",
"given_name": "Antonia"
},
{
"family_name": "Gantner",
"given_name": "Carlos W."
},
{
"family_name": "Mandelbaum",
"given_name": "Rachel S."
},
{
"family_name": "Paulson",
"given_name": "Richard J."
},
{
"family_name": "Lam",
"given_name": "Lisa"
},
{
"family_name": "Chou",
"given_name": "Tsui-Fen",
"orcid": "0000-0003-2410-2186",
"clpid": "Chou-Tsui-Fen"
},
{
"family_name": "Slavov",
"given_name": "Nikolai"
},
{
"family_name": "Zernicka-Goetz",
"given_name": "Magdalena",
"orcid": "0000-0002-7004-2471",
"clpid": "Zernicka-Goetz-M"
}
],
"abstract": "While non-mammalian embryos often rely on spatial pre-patterning, mammalian development has long been thought to begin with equivalent blastomeres. However, emerging evidence challenges this. Here, using multiplexed and label-free single-cell proteomics, we identify over 300 asymmetrically abundant proteins—many involved in protein degradation and transport—dividing mouse 2-cell-stage blastomeres into two distinct clusters, which we term alpha and beta. These proteomic asymmetries are detectable as early as the zygote stage, intensify by the 4-cell stage, and correlate with the sperm entry site, implicating fertilization as a symmetry-breaking event. Splitting 2-cell-stage embryos into halves reveals that beta blastomeres possess greater developmental potential than alpha blastomeres. Similar clustering and protein enrichment patterns found in human 2-cell embryos suggest this early asymmetry might be conserved. These findings uncover a previously unrecognized proteomic pre-patterning triggered by fertilization in mammalian embryos, with important implications for understanding totipotency and early lineage bias.
",
"doi": "10.1016/j.cell.2025.11.006",
"issn": "0092-8674",
"publisher": "Cell Press",
"publication": "Cell",
"publication_date": "2025-12-03"
},
{
"id": "authors:wn4wr-xfb87",
"collection": "authors",
"collection_id": "wn4wr-xfb87",
"cite_using_url": "https://authors.library.caltech.edu/records/wn4wr-xfb87",
"type": "article",
"title": "The first two blastomeres contribute unequally to the human embryo",
"author": [
{
"family_name": "Junyent",
"given_name": "Sergi",
"orcid": "0000-0003-2405-5885",
"clpid": "Junyent-Sergi"
},
{
"family_name": "Meglicki",
"given_name": "Maciej",
"orcid": "0009-0000-9224-3795",
"clpid": "Meglicki-Maciej"
},
{
"family_name": "Vetter",
"given_name": "Roman",
"orcid": "0000-0003-2901-7036",
"clpid": "Vetter-Roman"
},
{
"family_name": "Mandelbaum",
"given_name": "Rachel"
},
{
"family_name": "King",
"given_name": "Catherine",
"orcid": "0009-0004-8477-1212",
"clpid": "King-Catherine"
},
{
"family_name": "Patel",
"given_name": "Ekta M.",
"clpid": "Patel-Ekta-M"
},
{
"family_name": "Iwamoto-Stohl",
"given_name": "Lisa",
"orcid": "0000-0003-0776-054X",
"clpid": "Iwamoto-Stohl-Lisa"
},
{
"family_name": "Reynell",
"given_name": "Clare",
"orcid": "0000-0003-2733-3334",
"clpid": "Reynell-Clare"
},
{
"family_name": "Chen",
"given_name": "Dong-Yuan",
"orcid": "0000-0003-2179-2847",
"clpid": "Chen-Dong-Yuan"
},
{
"family_name": "Rubino",
"given_name": "Patrizia",
"orcid": "0000-0002-1701-3946",
"clpid": "Rubino-Patrizia"
},
{
"family_name": "Arrach",
"given_name": "Nabil",
"orcid": "0000-0002-0803-9626",
"clpid": "Arrach-Nabil"
},
{
"family_name": "Paulson",
"given_name": "Richard J.",
"clpid": "Paulson-Richard-J"
},
{
"family_name": "Iber",
"given_name": "Dagmar"
},
{
"family_name": "Zernicka-Goetz",
"given_name": "Magdalena",
"orcid": "0000-0002-7004-2471",
"clpid": "Zernicka-Goetz-M"
}
],
"abstract": "\n
\n
\n
\n
Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.
\n
\n
\n
\n
\n
Stem cell-based mammalian embryo models facilitate the discovery of developmental mechanisms because they are more amenable to genetic and epigenetic perturbations than natural embryos. Here, we highlight exciting recent advances that have yielded a plethora of models of embryonic development. Imperfections in these models highlight gaps in our current understanding and outline future research directions, ushering in an exciting new era for embryology.
",
"doi": "10.1016/j.gde.2023.102134",
"issn": "0959-437X",
"publisher": "Elsevier",
"publication": "Current Opinion in Genetics & Development",
"publication_date": "2024-02",
"volume": "84",
"pages": "102134"
}
]