Journal
DEVELOPMENT
Volume 142, Issue 23, Pages 4010-4025Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.122846
Keywords
Human embryo; Blastomere; Human embryonic stem cell; Human trophoblast stem cell; Fate specification; Transcriptome; Epigenome
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Funding
- California Institute for Regenerative Medicine [RC1-00113, RL1-00648, RT1-01108, CL1-00502, TR1-01250, RN2-00931-1, RM1-01703]
- Sandier Family Foundation
- Millipore Foundation
- Esther O'Keefe Foundation
- Autism Speaks, Dennis Weatherstone Fellowship
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Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines (designated UCSFBI-10) from single blastomeres of four 8-cell embryos and one 12-cell embryo from a single couple. Compared with numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation patterns that were, in part, indicative of trophoblast competence. At a transcriptional level, UCSFB lines from different embryos were often more closely related than those from the same embryo. As predicted by the transcriptomic data, immunolocalization of EOMES, T brachyury, GDF15 and active beta-catenin revealed differential expression among blastomeres of 8- to 10-cell human embryos. The UCSFB lines formed derivatives of the three germ layers and CDX2-positive progeny, from which we derived the first human trophoblast stem cell line. Our data suggest heterogeneity among early-stage blastomeres and that the UCSFB lines have unique properties, indicative of a more immature state than conventional lines.
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