多能干细胞变全能

2014/9/29 9:46:53 本站原创 佚名 【字体:

 

科学家们通过一种新方法表达了两种不同的基因,NANOGKLF2,它们具有重置细胞的功能。然后,他们通过抑制特定的生物学途径不停的重设细胞,最终形成的细胞能够分化成各种类型的细胞。

Researchers have resolved a long-standing challenge in stem cell biology by successfully 'resetting' human pluripotent stem cells to a fully pristine state, at a point of their greatest developmental potential.

 

Researchers at EMBL-EBI have resolved a long-standing challenge in stem cell biology by successfully 'resetting' human pluripotent stem cells to a fully pristine state, at point of their greatest developmental potential. The study, published in Cell, involved scientists from the UK, Germany and Japan and was led jointly by EMBL-EBI and the University of Cambridge.

 

 

"Reverting mouse cells to a completely 'blank slate' has become routine, but generating equivalent naïve human cell lines has proven far more challenging," says Dr Paul Bertone, Research Group Leader at EMBL-EBI and a senior author on the study.

 

At this point, subtle changes in gene expression begin to influence the cells, which are then considered 'primed' towards a particular lineage. Although pluripotent human cells can be cultured from in vitro fertilised (IVF) embryos, until now there have been no human cells comparable to those obtained from the mouse.

 

Taking a new approach, the scientists used reprogramming methods to express two different genes, NANOG and KLF2, which reset the cells. They then maintained the cells indefinitely by inhibiting specific biological pathways. The resulting cells are capable of differentiating into any adult cell type, and are genetically normal.

 

Together with Professor Wolf Reik at the Babraham Institute, the researchers also showed that DNA methylation (biochemical marks that influence gene expression) was erased over much of the genome, indicating that reset cells are not restricted in the cell types they can produce. In this more permissive state, the cells no longer retain the memory of their previous lineages and revert to a blank slate with unrestricted potential to become any adult cell.

 

The discovery paves the way for the production of superior patient material for translational medicine. Reset cells mark a significant advance for human stem cell applications, such as drug screening of patient-specific cells, and are expected to provide reliable sources of specialised cell types for regenerative tissue grafts.

 

Reference:

1.Yasuhiro Takashima, Ge Guo, Remco Loos, Jennifer Nichols, Gabriella Ficz, Felix Krueger, David Oxley, Fatima Santos, James Clarke, William Mansfield, Wolf Reik, Paul Bertone, Austin Smith. Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human. Cell, 2014; 158 (6): 1254 DOI: 10.1016/j.cell.2014.08.029

 

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