[ { "id": "authors:sexh8-37h83", "collection": "authors", "collection_id": "sexh8-37h83", "cite_using_url": "https://authors.library.caltech.edu/records/sexh8-37h83", "type": "article", "title": "Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification", "author": [ { "family_name": "Lamba", "given_name": "Adiyant", "orcid": "0000-0001-5389-1730" }, { "family_name": "Zhu", "given_name": "Meng", "orcid": "0000-0001-6157-8840" }, { "family_name": "Meglicki", "given_name": "Maciej", "orcid": "0009-0000-9224-3795" }, { "family_name": "Czukiewska", "given_name": "Sylwia", "orcid": "0000-0001-9151-9008" }, { "family_name": "Balasubramaniam", "given_name": "Lakshmi", "orcid": "0000-0001-6881-8261" }, { "family_name": "Hadas", "given_name": "Ron", "orcid": "0000-0001-9301-6607", "clpid": "Hadas-Ron" }, { "family_name": "Weishaupt", "given_name": "Nina" }, { "family_name": "Patel", "given_name": "Ekta M", "clpid": "Patel-Ekta-M" }, { "family_name": "Kavanagh", "given_name": "Yu Hua", "orcid": "0009-0004-0882-6998" }, { "family_name": "Wang", "given_name": "Ran" }, { "family_name": "Jing", "given_name": "Naihe", "orcid": "0000-0003-1509-6378" }, { "family_name": "Zernicka-Goetz", "given_name": "Magdalena", "orcid": "0000-0002-7004-2471", "clpid": "Zernicka-Goetz-M" } ], "abstract": "The first lineage allocation in mouse and human embryos separates the inner cell mass (ICM) from the outer trophectoderm (TE). This symmetry-breaking event is executed through polarization of cells at the 8 cell stage and subsequent asymmetric divisions, generating polar (TE) and apolar (ICM) cells. Here, we show that mouse embryo polarization is unexpectedly asynchronous. Cells polarizing at the early and late 8 cell stage have distinct molecular and morphological properties that direct their following lineage specification, with early polarizing cells being biased towards producing the TE lineage. More recent studies have also implicated heterogeneities between cells prior to the 8 cell stage in the first lineage allocation: cells exhibiting reduced methyltransferase CARM1 activity at the 4 cell stage are predisposed towards the TE fate. Here, we demonstrate that reduced CARM1 activity and upregulation of its substrate BAF155 promote early polarization and TE specification. These findings provide a link between asymmetries at the 4 cell stage and polarization at the 8 cell stage, mechanisms of the first lineage allocation that had been considered separate.", "doi": "10.7554/elife.101140", "issn": "2050-084X", "publisher": "eLife Sciences Publications, Ltd", "publication": "eLife", "publication_date": "2025-12-08", "volume": "13", "pages": "RP101140" }, { "id": "authors:ykz2r-3p577", "collection": "authors", "collection_id": "ykz2r-3p577", "cite_using_url": "https://authors.library.caltech.edu/records/ykz2r-3p577", "type": "article", "title": "Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development", "author": [ { "family_name": "Lau", "given_name": "Kasey Y. C.", "clpid": "Lau-Kasey-Y-C" }, { "family_name": "Rubinstein", "given_name": "Hernan", "clpid": "Rubinstein-Hernan" }, { "family_name": "Gantner", "given_name": "Carlos W.", "orcid": "0000-0003-0825-7786", "clpid": "Gantner-Carlos-W" }, { "family_name": "Hadas", "given_name": "Ron", "orcid": "0000-0001-9301-6607", "clpid": "Hadas-Ron" }, { "family_name": "Amadei", "given_name": "Gianluca" }, { "family_name": "Stelzer", "given_name": "Yonatan", "orcid": "0000-0001-9207-1479", "clpid": "Stelzer-Yonatan" }, { "family_name": "Zernicka-Goetz", "given_name": "Magdalena", "orcid": "0000-0002-7004-2471", "clpid": "Zernicka-Goetz-M" } ], "abstract": "

Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure.

", "doi": "10.1016/j.stem.2022.08.013", "pmcid": "PMC9648694", "issn": "1934-5909", "publisher": "Cell Press", "publication": "Cell Stem Cell", "publication_date": "2022-10-06", "series_number": "10", "volume": "29", "issue": "10", "pages": "1445-1458.e8" }, { "id": "authors:b2j0f-2xk53", "collection": "authors", "collection_id": "b2j0f-2xk53", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221122-564647900.8", "type": "article", "title": "Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development", "author": [ { "family_name": "Lau", "given_name": "Kasey Y. C.", "clpid": "Lau-Kasey-Y-C" }, { "family_name": "Rubinstein", "given_name": "Hernan", "clpid": "Rubinstein-Hernan" }, { "family_name": "Gantner", "given_name": "Carlos W.", "orcid": "0000-0003-0825-7786", "clpid": "Gantner-Carlos-W" }, { "family_name": "Hadas", "given_name": "Ron", "orcid": "0000-0001-9301-6607", "clpid": "Hadas-Ron" }, { "family_name": "Amadei", "given_name": "Gianluca", "orcid": "0000-0001-5405-968X", "clpid": "Amadei-Gianluca" }, { "family_name": "Stelzer", "given_name": "Yonatan", "orcid": "0000-0001-9207-1479", "clpid": "Stelzer-Yonatan" }, { "family_name": "Zernicka-Goetz", "given_name": "Magdalena", "orcid": "0000-0002-7004-2471", "clpid": "Zernicka-Goetz-M" } ], "abstract": "Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure.", "doi": "10.1016/j.stem.2022.08.013", "pmcid": "PMC9648694", "issn": "1934-5909", "publisher": "Cell Press", "publication": "Cell Stem Cell", "publication_date": "2022-10-06", "series_number": "10", "volume": "29", "issue": "10", "pages": "1445-1458.e8" } ]