Preimplantation embryo development is highly complex. Cells must manage changes to potency, cell positioning, and lineage specific gene expression. The embryo must first differentiate between inside and outside cells, where inside cells remain pluripotent (able to become any cell within the organism), and the outside cells lose potency to become multipotent stem cells (able to become only a few cell types). The differentiation of outside cells relies partially on the inactivation of the HIPPO signaling pathway that drives expression of the protein CDX2 in outside cells. Inside cells have active HIPPO signaling, maintain pluripotency and express SOX2. However, it is unknown how specific HIPPO pathway members like YAP1/WWTR1 regulate expression of these lineage-specific proteins. The second cell fate decision differentiates the inside cells into pluripotent epiblast and multipotent primitive endoderm. Transcription factor OCT4 has previously been shown to be necessary for development of both cell types. This dual requirement of OCT4 in two distinct lineages raises the question, how can OCT4 drive two cell different cell fates simultaneously. OCT4 has previously been shown to work with cofactors like SOX2, which is specific to pluripotent epiblast, so I hypothesized that OCT4 may also work with the primitive endoderm specific factor GATA6. My transcriptome analysis showed that OCT4 and GATA6 repress trophectoderm gene transcripts in the inner cell mass (ICM), which may help indirectly drive primitive endoderm fate. Additionally, I noted that loss of GATA6 and OCT4 caused reduced expression of trophectoderm specific factor CDX2 in early blastocyst and mid-blastocyst stages, respectively. Gata6 null mid-blastocyst stage embryos also exhibited prolonged OCT4 expression in the trophectoderm, indicating a novel and stage specific role for OCT4 and GATA6 in regulating trophectoderm gene expression.
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