title: Human embryonic stem cells express elevated levels of multiple pro-apoptotic BCL-2 family members.
abstract: Two of the greatest challenges in regenerative medicine today remain (1) the ability to culture human embryonic stem cells (hESCs) at a scale sufficient to satisfy clinical demand and (2) the ability to eliminate teratoma-forming cells from preparations of cells with clinically desirable phenotypes. Understanding the pathways governing apoptosis in hESCs may provide a means to address these issues. Limiting apoptosis could aid scaling efforts, whereas triggering selective apoptosis in hESCs could eliminate unwanted teratoma-forming cells. We focus here on the BCL-2 family of proteins, which regulate mitochondrial-dependent apoptosis. We used quantitative PCR to compare the steady-state expression profile of all human BCL-2 family members in hESCs with that of human primary cells from various origins and two cancer lines. Our findings indicate that hESCs express elevated levels of the pro-apoptotic BH3-only BCL-2 family members NOXA, BIK, BIM, BMF and PUMA when compared with differentiated cells and cancer cells. However, compensatory expression of pro-survival BCL-2 family members in hESCs was not observed, suggesting a possible explanation for the elevated rates of apoptosis observed in proliferating hESC cultures, as well as a mechanism that could be exploited to limit hESC-derived neoplasms.
authors.affiliation: College of Pharmacy, Touro University - California, Vallejo, California, United States of America. david.madden.tu@gmail.com
authors.forename: David T
authors.initials: DT
authors.lastname: Madden
authors.forename: Diana
authors.initials: D
authors.lastname: Davila-Kruger
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bredesen
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D002470:Cell Survival; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020043:Genes, Essential / Q000235:genetics; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2