MUC1* ligand, NM23-H1, is a novel growth factor that maintains human stem cells in a more naïve state.
oleh: Benoit J Smagghe, Andrew K Stewart, Mark G Carter, Laura M Shelton, Kyle J Bernier, Eric J Hartman, Amy K Calhoun, Vasilios M Hatziioannou, Gabriele Lillacci, Brian A Kirk, Brian A DiNardo, Kenneth S Kosik, Cynthia Bamdad
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2013-01-01 |
Deskripsi
We report that a single growth factor, NM23-H1, enables serial passaging of both human ES and iPS cells in the absence of feeder cells, their conditioned media or bFGF in a fully defined xeno-free media on a novel defined, xeno-free surface. Stem cells cultured in this system show a gene expression pattern indicative of a more "naïve" state than stem cells grown in bFGF-based media. NM23-H1 and MUC1* growth factor receptor cooperate to control stem cell self-replication. By manipulating the multimerization state of NM23-H1, we override the stem cell's inherent programming that turns off pluripotency and trick the cells into continuously replicating as pluripotent stem cells. Dimeric NM23-H1 binds to and dimerizes the extra cellular domain of the MUC1* transmembrane receptor which stimulates growth and promotes pluripotency. Inhibition of the NM23-H1/MUC1* interaction accelerates differentiation and causes a spike in miR-145 expression which signals a cell's exit from pluripotency.