title: Inducible Lentivirus-Mediated Expression of the Oct4 Gene Affects Multilineage Differentiation of Adult Human Bone Marrow-Derived Mesenchymal Stem Cells.
abstract: The octamer-binding transcription factor 4 (Oct4) gene plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) and reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs). In the present study, we transduced human bone marrow-derived mesenchymal stem cells (hMSCs) using tetracycline-on (Tet-On) lentiviruses carrying human Oct4 to examine the effects of regulated expression of human Oct4 on the proliferation and differentiation of hMSCs. hMSCs were efficiently transduced by Tet-On lentiviruses to express regulated levels of human Oct4 with doxycycline (Dox), as examined by immunofluorescent staining, flow cytometry, and quantitative real time-PCR (qRT-PCR) assays. Ectopic expression of Oct4 in transduced hMSCs increased the ability of colony formation. Continued expression of Oct4 further enhanced adipogenic differentiation of hMSCs, and transient expression of Oct4 sufficiently enhanced osteogenic differentiation of hMSCs. qRT-PCR analysis showed that ectopic expression of Oct4 in transduced hMSCs temporally increased the expression of Sox2 and c-Myc. Interestingly, ectopic expression of Oct4 reduced neuronal differentiation of hMSCs when incubated under neuronal differentiation conditions. Our results suggest that ectopic expression of human Oct4 leads to temporal changes in multilineage differentiation of hMSCs and may inhibit neuronal differentiation of hMSCs.
authors.affiliation: 1 Department of Anatomy, Capital Medical University , Beijing, 100069, China .
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.affiliation: 1 Department of Anatomy, Capital Medical University , Beijing, 100069, China .
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: An
authors.affiliation: 1 Department of Anatomy, Capital Medical University , Beijing, 100069, China .
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.affiliation: 1 Department of Anatomy, Capital Medical University , Beijing, 100069, China .
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: 1 Department of Anatomy, Capital Medical University , Beijing, 100069, China .
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.affiliation: 2 Department of Psychiatry, College of Medicine, University of Illinois at Chicago , Chicago, IL, 60612.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Qu
authors.affiliation: 3 Department of Neurosurgery, Upstate Medical University , Syracuse, NY, 13210.
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: Zhao
authors.affiliation: 1 Department of Anatomy, Capital Medical University , Beijing, 100069, China .|4 Center of Parkinson's Disease, Beijing Institute for Brain Disorders , Beijing, 100069, China .
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Duan
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D002454:Cell Differentiation; D000066630:Ectopic Gene Expression; D005434:Flow Cytometry; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014161:Transduction, Genetic
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human