Albumin-associated lipids regulate human embryonic stem cell self-renewal.
BACKGROUND
Although human embryonic stem cells (hESCs) hold great promise as a source of differentiated cells to treat several human diseases, many obstacles still need to be surmounted before this can become a reality. First among these, a robust chemically-defined system to expand hESCs in culture is still unavailable despite recent advances in the understanding of factors controlling hESC self-renewal.


RESULTS
In this study, we attempted to find new molecules that stimulate long term hESC self-renewal. In order to do this, we started from the observation that a commercially available serum replacement product has a strong positive effect on the expansion of undifferentiated hESCs when added to a previously reported chemically-defined medium. Subsequent experiments demonstrated that the active ingredient within the serum replacement is lipid-rich albumin. Furthermore, we show that this activity is trypsin-resistant, strongly suggesting that lipids and not albumin are responsible for the effect. Consistent with this, lipid-poor albumin shows no detectable activity. Finally, we identified the major lipids bound to the lipid-rich albumin and tested several lipid candidates for the effect.


CONCLUSIONS
Our discovery of the role played by albumin-associated lipids in stimulating hESC self-renewal constitutes a significant advance in the knowledge of how hESC pluripotency is maintained by extracellular factors and has important applications in the development of increasingly chemically defined hESC culture systems.
Garcia-Gonzalo
Francesc R
FR
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.
Izpisúa Belmonte
Juan Carlos
JC
D000418:Albumins / Q000502:physiology*; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008055:Lipids / Q000502:physiology*; D008970:Molecular Weight; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000418:Albumins; D017931:DNA Primers; D008055:Lipids