Pluripotent reprogramming of fibroblasts by lentiviral mediated insertion of SOX2, C-MYC, and TCL-1A.
Reprogramming of somatic cells to pluripotency promises to boost cellular therapy. Most instances of direct reprogramming have been achieved by forced expression of defined exogenous factors using multiple viral vectors. The most used 4 transcription factors, octamer-binding transcription factor 4 (OCT4), (sex determining region Y)-box 2 (SOX2), Kruppel-like factor 4 (KLF4), and v-myc myelocytomatosis viral oncogene homolog (C-MYC), can induce pluripotency in mouse and human fibroblasts. Here, we report that forced expression of a new combination of transcription factors (T-cell leukemia/lymphoma protein 1A [TCL-1A], C-MYC, and SOX2) is sufficient to promote the reprogramming of human fibroblasts into pluripotent cells. These 3-factor pluripotent cells are similar to human embryonic stem cells in morphology, in the ability to differentiate into cells of the 3 embryonic layers, and at the level of global gene expression. Induced pluripotent human cells generated by a combination of other factors will be of great help for the understanding of reprogramming pathways. This, in turn, will allow us to better control cell-fate and apply this knowledge to cell therapy.
Picanço-Castro
Virgínia
V
Center for Cell Therapy and Regional Blood Center, Ribeirão Preto, Brazil . v.picanco@hemocentro.fmrp.usp.br
Russo-Carbolante
Elisa
E
Reis
Luiza Cunha Junqueira
LC
Fraga
Ana Maria
AM
de Magalhães
Danielle Aparecida Rosa
DA
Orellana
Maristela Delgado
MD
Panepucci
Rodrigo Alexandre
RA
Pereira
Lygia Veiga
LV
Covas
Dimas Tadeu
DT
D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D004247:DNA / Q000235:genetics; D020405:Dermis / Q000166:cytology; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007700:Kinetics; D000090062:Kruppel-Like Factor 4; D016086:Lentivirus / Q000235:genetics*; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C090851:TCL1A protein, human; D004247:DNA