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Human ES Cell Culture Conditions Fail to Preserve the Mouse Epiblast State
A S Devika1, Anna Montebaur2,3, S Saravanan1
1Stem Cell Laboratory, Department of Genomic Science, Krishna Building, Central University of Kerala, Tejaswini Hills, Periye. P. O, Kasaragod District, Kerala 671316, India.
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.
Insights
Mouse embryonic stem cells (mESCs) do not stabilize in a primed state when exposed to human ESC or EpiSC conditions. Instead, prolonged exposure drives mESCs toward a primitive streak-like state, potentially via WNT signaling.
Area of Science:
- Developmental biology
- Stem cell biology
- Cellular reprogramming
Background:
- Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent distinct pluripotent states: naïve and primed, respectively.
- Culture conditions can influence the state of pluripotent stem cells (PSCs).
- Exposure to primed conditions can induce changes in mESCs.
Purpose of the Study:
- To investigate the stability of the undifferentiated epiblast state in mouse embryonic stem cells (mESCs) under primed culture conditions.
- To determine the fate of mESCs upon prolonged exposure to epiblast stem cell (EpiSC) or human ESC (hESC) culture conditions.
- To elucidate the underlying mechanisms driving potential state transitions.
Main Methods:
- Culture of mESCs under standard and primed (EpiSC/hESC) conditions.
- Analysis of cell state markers and gene expression profiles.
- Investigation of signaling pathways, including WNT signaling.
Main Results:
- Prolonged exposure of mESCs to EpiSC or hESC conditions does not stabilize a primed epiblast state.
- mESCs transition to a primitive streak (PS)-like state through an epiblast-like intermediate.
- The Brachyury-positive PS-like state appears to be promoted by endogenous WNT signaling.
Conclusions:
- The undifferentiated epiblast state is unstable in primed culture conditions.
- Mouse ESCs differentiate towards a primitive streak-like state rather than stabilizing in a primed state.
- Endogenous WNT signaling may play a crucial role in this transition, suggesting species-specific differences between mouse and human stem cells.
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