title: Plant hormones increase efficiency of reprogramming mouse somatic cells to induced pluripotent stem cells and reduce tumorigenicity.
abstract: Reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined pluripotency and self-renewal factors has taken stem cell technology to the forefront of regenerative medicine. However, a number of challenges remain in the field including efficient protocols and the threat of cancer. Reprogramming of plant somatic cells to plant embryonic stem cells using a combination of two plant hormones was discovered in 1957 and has been a routine university laboratory practical for over 30 years. The plant hormones responsible for cell reprogramming to pluripotency, indole-3-acetic acid (IAA) and isopentenyl adenosine (IPA), are present in human cells, leading to the exciting possibility that plant hormones might reprogram mammalian cells without genetic factors. We found that plant hormones on their own could not reprogram mammalian cells but increase the efficiency of the early formation of iPS cells combined with three defined genetic factors during the first 3 weeks of reprogramming by accelerating the cell cycle and regulating pluripotency genes. Moreover, the cytokinin IPA, a known human anticancer agent, reduced the threat of cancer of iPS cell in vitro by regulating key cancer and stem cell-related genes, most notably c-Myc and Igf-1. In conclusion, the plant hormones, auxin and cytokinin, are new small chemicals useful for enhancing early reprogramming efficiency of mammalian cells and reducing the threat of cancer from iPS cells. These findings suggest a novel role for plant hormones in the biology of mammalian cell plasticity.
authors.affiliation: 1 Molecular Genetics Research Group, Control of Pluripotency Laboratory, Department of Physiological Sciences I, Faculty of Medicine, University of Barcelona , Hospital Clinic, Barcelona, Spain .
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Alvarez Palomo
authors.forename: Samuel
authors.initials: S
authors.lastname: McLenachan
authors.forename: Jordi
authors.initials: J
authors.lastname: Requena Osete
authors.forename: Cristina
authors.initials: C
authors.lastname: Menchón
authors.forename: Carme
authors.initials: C
authors.lastname: Barrot
authors.forename: Fred
authors.initials: F
authors.lastname: Chen
authors.forename: Sergi
authors.initials: S
authors.lastname: Munné-Bosch
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edel
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics*; D003583:Cytokinins / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007210:Indoleacetic Acids / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010937:Plant Growth Regulators / Q000494:pharmacology*
chemical_list: D003583:Cytokinins; D007210:Indoleacetic Acids; D010937:Plant Growth Regulators