The role of EPASI, an oxygen-sensing transcription facor, in trophoblast differentiation

Braeden Rose

Document Type

Article

Publication Date

Summer 2023

Keywords

JGM

JAX Location

In: Student Reports, Summer 2023, The Jackson Laboratory

Abstract

EPAS1 is an oxygen-sensing transcription factor expressed most highly in lung and placental tissue. Oxygen concentrations are highly regulated in human development with the first trimester under low oxygen. Previous data from our lab indicates human induced pluripotent stem cells (hiPSCs) do not express EPAS1 and only do so once differentiated along the trophoblast lineage. We therefore hypothesized EPAS1’s importance in successful PrSyn and ExM differentiation. To test this, sets of hiPSCs with four different genotypes (one wildtype (wt) and three different knockout (KO) strategies) were differentiated at 3% and 20% oxygen. RT-qPCR results indicate that EPAS1 is expressed more in PrSyn than ExM in both hypoxia and normoxia. In hypoxic ExM, expression levels of COL3A1, LUM, and IGFBP7, ExM markers, are lower in KO lines than wt. Additionally, normoxic PrSyn KO lines express GCM1, SDC1, and GATA2, PrSyn markers, at levels lower than the wt. These data suggest EPAS1’s importance in PrSyn and ExM differentiation.

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