期刊
DEVELOPMENT
卷 142, 期 23, 页码 4010-4025出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.122846
关键词
Human embryo; Blastomere; Human embryonic stem cell; Human trophoblast stem cell; Fate specification; Transcriptome; Epigenome
资金
- 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
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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