MUC1*Ligand, NM23-H1, Is a Novel Growth Factor That Maintains Human Stem Cells in a More Naive State

作者：Smagghe Benoit J; Stewart Andrew K; Carter Mark G; Shelton Laura M; Bernier Kyle J; Hartman Eric J; Calhoun Amy K; Hatziioannou Vasilios M; Lillacci Gabriele; Kirk Brian A; DiNardo Brian A; Kosik Kenneth S; Bamdad Cynthia^*

来源：PLos One, 2013, 8(3): e58601.

DOI：10.1371/journal.pone.0058601

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 "naive" 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.

• 出版日期2013-3-7