title: Cell divisions are not essential for the direct conversion of fibroblasts into neuronal cells.
abstract: Direct lineage conversion is a promising approach for disease modeling and regenerative medicine. Cell divisions play a key role in reprogramming of somatic cells to pluripotency, however their role in direct lineage conversion is not clear. Here we used transdifferentiation of fibroblasts into neuronal cells by forced expression of defined transcription factors as a model system to study the role of cellular division in the direct conversion process. We have shown that conversion occurs in the presence of the cell cycle inhibitors aphidicolin or mimosine. Moreover, overexpression of the cell cycle activator cMyc negatively influences the process of direct conversion. Overall, our results suggest that cell divisions are not essential for the direct conversion of fibroblasts into neuronal cells.
authors.affiliation: a Institute of Cytology and Genetics ; Novosibirsk , Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Fishman
authors.forename: T A
authors.initials: TA
authors.lastname: Shnayder
authors.forename: K E
authors.initials: KE
authors.lastname: Orishchenko
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: N
authors.initials: N
authors.lastname: Alenina
authors.forename: O L
authors.initials: OL
authors.lastname: Serov
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects; D065150:Cellular Reprogramming; D004317:Doxorubicin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008898:Mimosine / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016590:Aphidicolin; D008898:Mimosine; D004317:Doxorubicin
keywords: BAM+M, Brn2, Ascl1, Myt1l and cMyc; BAM, Brn2, Ascl1 and Myt1l; DOX, doxycycline, BrdU, bromodeoxyuridine; ES cells, embryonic stem cells; MEF, mouse embryonic fibroblasts; cell division; direct conversion; fibroblast; iPS cells, induced pluripotent stem cells; neuron; reprogramming; transdifferentiation