February 11, 2008

First induced pluripotent stem cells (iPSC) created in California

Broad Stem Cell Research Center Scientists Reprogram Human Skin Cells Into Cells with the
Same Properties as Human Embryonic Stem Cells

UCLA Broad Stem Cell Research Center scientists Kathrin Plath, William Lowry, April Pyle, Amander Clark, and Rupa Sridharan, used genetic alteration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, which have the ability to become every cell type found in the human body. Four regulator genes were used to create the cells, called induced pluripotent stem cells or iPS cells. The article is published in PNAS, v105, n8: February 26, 2008.

June 2007

Nimet Maherali, Rupa Sridharan, Wei Xie, Jochen Utikal, Sarah Eminli, Katrin Arnold, Matthias Stadtfeld, Robin Yachechko, Jason Tchieu, Rudolf Jaenisch, Kathrin Plath*, and Konrad Hochedlinger, Directly Reprogrammed Fibroblasts Show Global Epigenetic Remodeling and Widespread Tissue Contribution,
Cell Stem Cell, Vol 1, 55-70, 07 June 2007.
Ectopic expression of the four transcription factors Oct4, Sox2, c-Myc, and Klf4 is sufficient to confer a pluripotent state upon the fibroblast genome, generating induced pluripotent stem (iPS) cells. It remains unknown if nuclear reprogramming induced by these four factors globally resets epigenetic differences between differentiated and pluripotent cells. Here, using novel selection approaches, we have generated iPS cells from fibroblasts to characterize their epigenetic state. Female iPS cells showed reactivation of a somatically silenced X chromosome and underwent random X inactivation upon differentiation. Genome-wide analysis of two key histone modifications indicated that iPS cells are highly similar to ES cells. Consistent with these observations, iPS cells gave rise to viable high-degree chimeras with contribution to the germline. These data show that transcription factor-induced reprogramming leads to the global reversion of the somatic epigenome into an ES-like state. Our results provide a paradigm for studying the epigenetic modifications that accompany nuclear reprogramming and suggest that abnormal epigenetic reprogramming does not pose a problem for the potential therapeutic applications of iPS cells. See the complete Cell Stem Cell article.
* corresponding author

Yin Shen, Janet Chow, Zunde Wang, and Guoping Fan: Abnormal CpG Island Methylation Occurs During in vitro Differentiation of Human Embryonic Stem Cells
Human Molecular Genetics, 2006, v15, n17
ISCBM scientists found that neural stem cells grown from one of the federally approved human embryonic stem cell lines proved to be inferior to neural stem cells derived from fetal tissue donated for research. Dr. Guoping Fan and associates coaxed cells from the federally approved line to differentiate into neural stem cells, a process that might one day be used to grow replacement cells to treat such debilitating  diseases as Parkinson’s and Alzheimer’s. However, the neural stem cells had an abnormality in a gene called CPT 1A that inhibited expression, a metabolic condition that causes hypoglycemia in humans.The study appears this week in an early online edition of the journal Human Molecular Genetics