Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors

Abstract

Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4 (refs 1-11). Considering that ectopic expression of c-Myc causes tumorigenicity in offspring and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells. These two-factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.

Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

“…Among the four factors, c-Myc is not necessary for the reprogramming of somatic cells into iPSCs [45,46]. Furthermore, recent studies have shown that both mouse and human neural stem cells can be reprogrammed to iPSCs with Oct4 and Klf4, or Oct4 alone [47][48][49]. However, neural stem cells express endogenous Sox2, suggesting that Sox2 and Oct4 are sufficient for iPSC induction, while Klf4 and c-Myc may act to enhance the efficiency of this induction.…”

Embryonic stem cell markers expression in cancers

“…The ability of Myc to bind to a staggeringly large number of genomic loci has also been demonstrated in ES cells [16] and is likely to underlie its activity as part of the "magic quartet" of transcription factors that can reprogram somatic cells to pluripotency [1; 17; 18; 19]. High levels of Myc may block cell differentiation and enhance self-renewal of committed and differentiated cells [20].…”

Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis

“…For example, neural stem cells were successfully re-programmed by using only oct4 and klf4 transcription factors upon determining that these cells already present sox2 and c-myc. 31 It seems that endogenous expression levels of transcription factor genes such as oct4, klf4, sox2 and c-myc in adult cells are very important for re-programming adult cells to induced pluri-potent stem cells. 29 The expression levels of these genes have not yet been characterized in human tooth germ stem cells (hTGSCs).…”