Generation of Induced Pluripotent Stem Cells from Human Cord Blood Using OCT4 and SOX2

Giorgetti, Alessandra; Montserrat, Núria; Aasen, Trond; González, Federico; Rodríguez-Pizá, Ignacio; Vassena, Rita; Raya, Ángel; Boué, Stéphanie; Barrero, María J.; Corbella, Begoña Aran; Torrabadella, M; Veiga, Anna; Belmonte, Juan Carlos Izpisúa

doi:10.1016/j.stem.2009.09.008

Cited by 379 publications

(282 citation statements)

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“…It has been previously shown that stem cell populations are more amenable to reprogramming than other somatic cells, probably as a result of their preexisting epigenetic state (14,15). Moreover, because of their biological characteristics and availability, CB cells as a donor cell type could offer clear logistic advantages vs. other adult somatic cell types (16,17).…”

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confidence: 99%

Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc

Giorgetti

Marchetto

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcription factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133 + cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, and electrophysiological analysis show that CBiNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers. CB-iNCs show the ability to fire action potentials after in vitro maturation as well as after in vivo transplantation into the mouse hippocampus. This system highlights the potential of CB cells and offers an alternative means to the study of cellular plasticity, possibly in the context of drug screening research and of future cell-replacement therapies.neurons | reprogramming | stem cells T he fate of adult somatic cells is not fixed rigidly and can be reprogrammed by experimental manipulation. The generation of induced pluripotent stem cells (iPSCs) represents the most dramatic evidence that the epigenome of somatic cells are remarkably plastic (1). Recently, it has been reported that fibroblasts can be converted by ectopic expression of defined transcription factors into postmitotic neurons (2-9), neural progenitors (10, 11), and self-renewing neural stem cells (NSCs) (12, 13). However, most reported methods rely on the use of multiple transcription factors and the use of fibroblasts as donor cells.Here we investigate if cord blood (CB) stem cells can be induced to acquire a neuronal phenotype by using only one transcription factor. It has been previously shown that stem cell populations are more amenable to reprogramming than other somatic cells, probably as a result of their preexisting epigenetic state (14,15). Moreover, because of their biological characteristics and availability, CB cells as a donor cell type could offer clear logistic advantages vs. other adult somatic cell types (16,17). These cells can be collected without any risk for the donor and are young cells carrying minimal somatic mutations.Strikingly, we show that forced expression of Sox2 is sufficient to convert CB CD133 + cells into induced neuronal progenitor (NP)-like cells, a conversion process that is augmented by the coexpression of c-Myc. Sox2 is highly expressed in adult NSCs, is one of the earliest functional markers of neuroectodermal specification in the embryo, and plays a key role in the neural lineage specification (18)(19)(20). We show that Sox2-transduced CB cells acquire a distinct neuronal morphology and express multiple neuronal markers in vitro, and that they can be expanded for as many as 25 passages when cultured in permissive condition culture. Moreover, we show that CB-induced neuronal-like cells (CB-iNCs) are able to differentiate in vitro and ...

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confidence: 99%

Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc

Giorgetti

Marchetto

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…63 For therapeutic usage, it is important to minimize the number of genes transduced into somatic cells to generate iPSCs. 64 However, decreasing the number of TFs leads to decreased iPSC generation efficiency. Therefore, several small molecules have been developed to enhance the generation efficiency of iPSCs.…”

Section: Small Molecules That Promote Ipsc Production Involving Few Tfsmentioning

confidence: 99%

Generation of pluripotent stem cells without the use of genetic material

Higuchi

Ling

Kumar

et al. 2015

Laboratory Investigation

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Induced pluripotent stem cells (iPSCs) provide a platform to obtain patient-specific cells for use as a cell source in regenerative medicine. Although iPSCs do not have the ethical concerns of embryonic stem cells, iPSCs have not been widely used in clinical applications, as they are generated by gene transduction. Recently, iPSCs have been generated without the use of genetic material. For example, protein-induced PSCs and chemically induced PSCs have been generated by the use of small and large (protein) molecules. Several epigenetic characteristics are important for cell differentiation; therefore, several small-molecule inhibitors of epigenetic-modifying enzymes, such as DNA methyltransferases, histone deacetylases, histone methyltransferases, and histone demethylases, are potential candidates for the reprogramming of somatic cells into iPSCs. In this review, we discuss what types of small chemical or large (protein) molecules could be used to replace the viral transduction of genes and/or genetic reprogramming to obtain human iPSCs.

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“…hematopoietic progenitor cells to iPSCs [144,154]. However, the low amount of CD34+ cells in peripheral blood (estimated less than 0.1%) is a key factor limiting the availability of these cells for reprogramming.…”

Section: Cytokine Signaling Pathways Regulating Pluripotencymentioning

confidence: 99%