Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification

• Published in: Development (Cambridge) Vol. 142; no. 23; pp. 4010 - 4025
• Main Authors: Zdravkovic, Tamara, Nazor, Kristopher L, Larocque, Nicholas, Gormley, Matthew, Donne, Matthew, Hunkapillar, Nathan, Giritharan, Gnanaratnam, Bernstein, Harold S, Wei, Grace, Hebrok, Matthias, Zeng, Xianmin, Genbacev, Olga, Mattis, Aras, McMaster, Michael T, Krtolica, Ana, Valbuena, Diana, Simón, Carlos, Laurent, Louise C, Loring, Jeanne F, Fisher, Susan J
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists 01-12-2015
• Subjects: beta Catenin - metabolism; Blastocyst - cytology; Blastomeres - cytology; Cell Differentiation; Cell Line; Cell Lineage; DNA Methylation; Embryo Culture Techniques; Embryonic Stem Cells - cytology; Endoderm - metabolism; Fibroblasts - metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; Growth Differentiation Factor 15 - metabolism; Humans; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Neural Stem Cells - cytology; Oligonucleotide Array Sequence Analysis; Stem Cells and Regeneration; Transcription, Genetic; Transcriptome; Trophoblasts - cytology; Human embryonic stem cell; Fate specification; Transcriptome; Human trophoblast stem cell; Blastomere; Epigenome; Human embryo
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.122846

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 UCSFB1-10) 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 β-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.