Abstract

Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) are the pluripotent stem cells (PSCs), derived from the inner cell mass (ICM) of preimplantation embryos at embryonic day 3.5 (E3.5) and postimplantation embryos at E5.5-E7.5, respectively. Depending on their environment, PSCs can exist in the so-called naïve (ESCs) or primed (EpiSCs) states. Exposure to EpiSC or human ESC (hESC) culture condition can convert mESCs towards an EpiSC-like state. Here, we show that the undifferentiated epiblast state is however not stabilized in a sustained manner when exposing mESCs to hESC or EpiSC culture condition. Rather, prolonged exposure to EpiSC condition promotes a transition to a primitive streak- (PS-) like state via an unbiased epiblast-like intermediate. We show that the Brachyury-positive PS-like state is likely promoted by endogenous WNT signaling, highlighting a possible species difference between mouse epiblast-like stem cells and human Embryonic Stem Cells.

Highlights

  • Pluripotency is the intrinsic, unrestricted, flexible developmental potential of the embryonic cells in a developing embryo, to give rise to the three embryonic germ layers, forming all the cells in an adult organism

  • We show that this condition matured the Mouse embryonic stem cells (mESCs) to distinct primed epiblast stem cells (EpiSCs)-like states, these states could not be sustained, but the cells further matured to a primitive streak (PS)/mesendoderm-like state, highlighting a possible species difference between mouse and human epiblast-like stem cells

  • Our results demonstrate that the primed EpiSC-like states that were derived by the exposure of naïve embryonic stem cells (ESCs) to A and FGF2 (AA/F2) are distinct from each other and from the EpiSCs used in this study

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Summary

Introduction

Pluripotency is the intrinsic, unrestricted, flexible developmental potential of the embryonic cells in a developing embryo, to give rise to the three embryonic germ layers, forming all the cells in an adult organism. This can be captured in vitro, by deriving pluripotent stem cells (PSCs) from various developmental stages. The PSCs, derived from the epiblast of preimplantation mouse embryos (E3.75-E4.5) are called embryonic stem cells (ESCs) [1,2,3]. The PSCs that are derived from the postimplantation embryos (E5.5-E7.5) are called the epiblast stem cells (EpiSCs), which are in a primed state of pluripotency [1, 8]. When the mESCs are exposed to the hESC/EpiSC condition (AA/F2), they transition to an EpiSC-like primed state [1, 8,9,10,11]

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