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GSE30127
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Placental trophoblasts are key determinants of in utero development. Mouse trophoblast stem cells (mTSCs), which were first derived over a decade ago, are a powerful cell culture model for studying their self-renewal or differentiation. Our attempts to isolate an equivalent population from the trophectoderm of human blastocysts generated colonies that quickly differentiated in vitro. This finding suggested that the human placenta has another progenitor niche. Here we show that the chorion is one such site. Initially, we immunolocalized pluripotency factors and trophoblast fate determinants in the early-gestation placenta, amnion and chorion. Immunoreactive cells were numerous in the chorion. We isolated these cells and plated them in medium containing FGF and an inhibitor of activin/nodal signaling, which is required for human embryonic SC self-renewal. Colonies of polarized cells with a limited lifespan emerged. Trypsin dissociation yielded continuously self-replicating monolayers. Colonies and monolayers formed the two major human trophoblast lineagesmultinucleate syncytiotrophoblasts and invasive cytotrophoblasts (CTBs). Transcriptional profiling experiments revealed the factors associated with the self-renewal or differentiation of human chorionic trophoblast progenitor cells (TBPCs). They included imprinted genes, NR2F1/2, HMGA2 and adhesion molecules that were required for TBPC differentiation. Together, the results of these experiments suggested that the chorion is one source of epithelial CTB progenitors. These findings explain why CTBs of fully formed chorionic villi have a modest mitotic index and identify the chorionic mesoderm as a niche for TBPCs that support placental growth.
Publication Title
Establishment of human trophoblast progenitor cell lines from the chorion.
Sample Metadata Fields
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View Samples- Homo sapiens
- 64 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Duplication of the genome in mammalian cells occurs in a defined temporal order referred as its replication-timing program (RT). RT is regulated in units of 400-800 Kb referred as replication domains (RDs) and changes dynamically during development. Changes in RT are generally coordinated with transcriptional competence and changes in sub-nuclear position. We generated genome-wide RT profiles for 29 distinct human cell types including embryonic stem cell (hESC)-derived, primary cells and established cell lines representing intermediate stages of endoderm, mesoderm, ectoderm and neural crest (NC) development. We identified clusters of RDs that replicate at unique times in each stage (RT signatures). Surprisingly, transcriptome data revealed that, despite an overall correlation between early replication and transcriptional activity, most genes that switched RT during differentiation can be expressed when late replicating. Intriguingly, this class of genes was nonetheless induced to high expression levels prior to a late to early RT switch and down-regulated after the switch back to late replication. These results clarify the complex relationship between transcription and RT and identify classes of genes that behave as potential drivers of the RT switch vs. those that may depend upon an RT switch for transcriptional induction.
Publication Title
Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.
Sample Metadata Fields
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