title: Culture environment-induced pluripotency of SACK-expanded tissue stem cells.
abstract: Previous efforts to improve the efficiency of cellular reprogramming for the generation of induced pluripotent stem cells (iPSCs) have focused mainly on transcription factors and small molecule combinations. Here, we report the results of our focus instead on the phenotype of the cells targeted for reprogramming. We find that adult mouse pancreatic tissue stem cells derived by the method of suppression of asymmetric cell kinetics (SACK) acquire increased potency simply by culture under conditions for the production and maintenance of pluripotent stem cells. Moreover, supplementation with the SACK agent xanthine, which promotes symmetric self-renewal, significantly increases the efficiency and degree of acquisition of pluripotency properties. In transplantation analyses, clonal reprogrammed pancreatic stem cells produce slow-growing tumors with tissue derivative of all three embryonic germ layers. This acquisition of pluripotency, without transduction with exogenous transcription factors, supports the concept that tissue stem cells are predisposed to cellular reprogramming, particularly when symmetrically self-renewing.
authors.affiliation: The Adult Stem Cell Technology Center and Programs in Regenerative Biology and Cancer Biology, Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Paré
authors.forename: James L
authors.initials: JL
authors.lastname: Sherley
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D005260:Female; D006651:Histocytochemistry; D018398:Homeodomain Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000473:pathology; D010179:Pancreas / Q000166:cytology; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D000469:Alkaline Phosphatase