Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency – University of Copenhagen

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10 August 2016

Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency

Publication

In this article, a collaboration between the KU transgenic unit and the Brickman lab at DanStem has lead to new insights into embryonic stem cell (ESC) culture and potential new experimental approaches.

Paper abstract:
Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i) or with knockout serum replacement (KOSR), but not serum, can generate high-level chimeras regardless of how these cells were derived. ESCs cultured in these conditions showed a transcriptional correlation with early pre-implantation embryos (E1.5–E3.5) and contributed to development from the 2-cell stage. Conversely, the transcriptome of serum-cultured ESCs correlated with later stages of development (E4.5), at which point embryonic cells are more restricted in their developmental potential. Thus, ESC culture systems are not equivalent, but support cell types that resemble distinct developmental stages. Cells derived in one condition can be reprogrammed to another developmental state merely by adaptation to another culture condition.

In this article, a collaboration between the University of Copenhagen transgenic Unit and the Brickman lab at DanStem has lead to new insights into embryonic stem cell (ESC) culture and potential new experimental approaches.  

Javier Martin Gonzalez and colleagues show that different ESC culture conditions select for unique combinations of embryo-like cells that resemble distinct developmental stages. ESC cells are normally pluripotent, able to make just the embryonic lineages, and under standard conditions resemble developmental stages that are no longer able to make extra-embryonic cell types like the placenta, but cells from earlier stages of development normally produce both embryonic and extra-embryonic tissues.  The Brickman group previously found that totipotent ESCs, cells that can make all lineages, could be generated in particular culture conditions. For this study, the KU transgenic unit produce new ESC lines from defined genetic backgrounds.  When these new ESCs were cultured in conditions that produce cells that resemble earlier development, they have the capacity to both clonally contribute to development, and differentiate into extraembryonic lineages in vivo and in vitro. This means that with these new ESC lines derived by the KU transgenic core were cultured in totipotent conditions, the authors were able to generate an entire mouse from a single ESC.


 Link to the publication

Martin Gonzalez, Javier, Sophie M Morgani, Robert A Bone, Kasper Bonderup, Sahar Abelchian, Cord Brakebusch & Joshua M Brickman (2016). Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency. Stem Cell Reports, 7(2), 177-191, doi:10.1016/j.stemcr.2016.07.009.