Species-specific developmental timing is maintained by pluripotent stem cells ex utero

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Genomics

Background:

• Control of species-specific developmental timing remains poorly understood.
• Pluripotent stem cells offer a model to study early development.
• In vitro differentiation protocols aim to recapitulate in vivo processes.

Purpose of the Study:

• To investigate whether pluripotent stem cells retain species-specific developmental timing in vitro.
• To compare the rates of differentiation between human embryonic stem cells and mouse epiblast stem cells.
• To identify potential molecular mechanisms underlying developmental timing differences.

Main Methods:

• Human embryonic stem (ES) cells and mouse epiblast stem (EpiS) cells were differentiated under identical neural induction conditions.
• Detailed RNA-sequencing time courses were performed to analyze gene expression profiles.
• Dynamic Time Warping analysis was used to compare gene regulation rates between species.

Main Results:

• Mouse EpiS cells exhibited accelerated gene expression profiles compared to human ES cells, reflecting in vivo developmental rates.
• Dynamic Time Warping identified 3389 genes regulated faster in mouse EpiS cells versus none in human ES cells.
• Human ES cells differentiated in teratomas maintained in vitro differentiation rates, irrespective of the mouse host environment.

Conclusions:

• Pluripotent stem cells possess an intrinsic, species-specific developmental clock.
• This cell-autonomous clock governs developmental timing even outside the intact embryo.
• The findings provide insights into the fundamental mechanisms of species-specific development.