Journal Article

Direct reprogramming of human neural stem cells by OCT4

Greber, Boris, Zaehres, Holm, Schöler, Hans R., Meyer, Johann, Park, Kook In, Araúzo-Bravo, Marcos J., Kim, Jeong Beom

2009

Overview

Human iPS cells made simpler Earlier this year Hans Schöler's group reported that a single transcription factor, OCT4 , was sufficient to reprogram mouse adult neural stem cells to pluripotency, making them capable of producing virtually any cell type in the right conditions. This was a striking simplification of the process — OCT4 was just one of four factors used in the early (2006/7) and classic work on producing iPS (induced pluripotent stem) cells. Now Schöler and colleagues show that OCT4 alone can also generate iPS cells from human neural stem cells. Although induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors, the expression of one of these four, Oct4 , is sufficient to directly reprogram adult mouse neural stem cells to iPS cells. The generation of one-factor human iPS cells from human fetal neural stem cells by ectopic expression of OCT4 alone is now reported, demonstrating that OCT4 is sufficient to reprogram human neural stem cells to pluripotency. Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors ( OCT4 (also called POU5F1 ), SOX2 , c-Myc and KLF4 ) 1 , 2 , 3 , 4 , 5 , 6 , 7 . We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells 8 . Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo . These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Biomarkers - analysis / Cell Dedifferentiation / Cell Differentiation / Cell Line / Cellular Reprogramming / DNA binding proteins / DNA Methylation / Embryonic stem cells / Embryonic Stem Cells - cytology / Embryonic Stem Cells - metabolism / Epigenesis, Genetic / Fetus - cytology / Gene expression / Gene Expression Profiling / Genetic aspects / Germ Layers - cytology / Germ Layers - metabolism / Humanities and Social Sciences / Humans / letter / Mice / multidisciplinary / Neurons / Neurons - cytology / Neurons - metabolism / Octamer Transcription Factor-3 - genetics / Octamer Transcription Factor-3 - metabolism / Physiological aspects / Pluripotent Stem Cells - cytology / Pluripotent Stem Cells - metabolism / Proteins / Science / Science (multidisciplinary) / Stem cells / Studies