title: Cyclin A1 is essential for setting the pluripotent state and reducing tumorigenicity of induced pluripotent stem cells.
abstract: The proper differentiation and threat of cancer rising from the application of induced pluripotent stem (iPS) cells are major bottlenecks in the field and are thought to be inherently linked to the pluripotent nature of iPS cells. To address this question, we have compared iPS cells to embryonic stem cells (ESCs), the gold standard of ground state pluripotency, in search for proteins that may improve pluripotency of iPS cells. We have found that when reprogramming somatic cells toward pluripotency, 1%-5% of proteins of 5 important cell functions are not set to the correct expression levels compared to ESCs, including mainly cell cycle proteins. We have shown that resetting cyclin A(1) protein expression of early-passage iPS cells closer to the ground state pluripotent state of mouse ESCs improves the pluripotency and reduces the threat of cancer of iPS cells. This work is a proof of principle that reveals that setting expression of certain proteins correctly during reprogramming is essential for achieving ESC-state pluripotency. This finding would be of immediate help to those researchers in different fields of iPS cell work that specializes in cell cycle, apoptosis, cell adhesion, cell signaling, and cytoskeleton.
authors.affiliation: Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Perth, Western Australia.
authors.forename: Samuel
authors.initials: S
authors.lastname: McLenachan
authors.forename: Cristina
authors.initials: C
authors.lastname: Menchón
authors.forename: Angel
authors.initials: A
authors.lastname: Raya
authors.forename: Antonella
authors.initials: A
authors.lastname: Consiglio
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edel
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D056750:Cyclin A1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D020543:Proteome / Q000378:metabolism; D034622:RNA Interference; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: C503745:CCNA1 protein, human; D056750:Cyclin A1; D020543:Proteome