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Development. 2015 Dec 1;142(23):4010-25. doi: 10.1242/dev.122846. Epub 2015 Oct 19.

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

Author information

1
Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA Division of Maternal Fetal Medicine, University of California San Francisco, San Francisco, CA 94143, USA Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA Human Embryonic Stem Cell Program, University of California San Francisco, San Francisco, CA 94143, USA.
2
Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA Division of Maternal Fetal Medicine, University of California San Francisco, San Francisco, CA 94143, USA Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA.
4
StemLifeLine, San Carlos, CA 94070, USA.
5
The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA.
6
The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
7
Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
8
Buck Institute for Research on Aging, Novato, CA 94945, USA.
9
The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
10
The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA Human Embryonic Stem Cell Program, University of California San Francisco, San Francisco, CA 94143, USA Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA.
11
Fundación Instituto Valenciano de Infertilidad (IVI), Parc Científic Universitat de València, 46980, Valencia, Spain.
12
Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA Department of Reproductive Medicine, University of California San Diego, La Jolla, CA 92093, USA.
13
Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA Division of Maternal Fetal Medicine, University of California San Francisco, San Francisco, CA 94143, USA Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA Human Embryonic Stem Cell Program, University of California San Francisco, San Francisco, CA 94143, USA Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA sfisher@cgl.ucsf.edu.

Abstract

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.

KEYWORDS:

Blastomere; Epigenome; Fate specification; Human embryo; Human embryonic stem cell; Human trophoblast stem cell; Transcriptome

PMID:
26483210
PMCID:
PMC4712832
DOI:
10.1242/dev.122846
[Indexed for MEDLINE]
Free PMC Article

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