6533b856fe1ef96bd12b1f13
RESEARCH PRODUCT
Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.
Matthias HebrokAna KrtolicaKristopher L. NazorMichael T. McmasterTamara ZdravkovicAras N. MattisXianmin ZengJeanne F. LoringLouise C. LaurentGnanaratnam GiritharanMatthew GormleyMatthew DonneNathan HunkapillarHarold S. BernsteinOlga GenbacevNicholas LarocqueDiana VabuenaSusan J. FisherCarlos SimónGrace Weisubject
BlastomeresTranscription GeneticCellular differentiationMedical and Health SciencesEmbryo Culture TechniquesEpigenomeNeural Stem CellsDevelopmentalMyocytes Cardiacbeta CateninOligonucleotide Array Sequence AnalysisEndodermGene Expression Regulation DevelopmentalEmbryoCell DifferentiationBiological SciencesStem Cells and RegenerationTrophoblastsmedicine.anatomical_structureembryonic structuresStem Cell Research - Nonembryonic - Non-HumanStem cellEndodermCardiacTranscriptionBrachyuryGrowth Differentiation Factor 151.1 Normal biological development and functioningBiologyCell LineGeneticUnderpinning researchmedicineGeneticsHumansHuman embryoCell LineageBlastocystMolecular BiologyEmbryonic Stem CellsMyocytesBlastomereHuman embryonic stem cellGene Expression ProfilingTrophoblastFibroblastsDNA MethylationStem Cell ResearchHuman trophoblast stem cellEmbryonic stem cellMolecular biology102Fate specificationBlastocystGene Expression RegulationGeneric health relevanceTranscriptomeDevelopmental Biologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-12-01 |