Researchers have discovered that environmental factors critically influence the growth of Induced Pluripotent Stem Cells (IPS cells) that are derived from adult skin cells. For the first time, researchers have shown that protein factors released by other cells affect the “reprogramming” of adult cells into stem cells.
“We’ve reinforced our hypothesis that the cell’s environment is vital to the reprogramming process,” said Gladstone Senior Investigator Shinya Yamanaka MD, PhD, a professor at UCSF. “We can now expand our understanding of cell development — and use iPS cells to model conditions such as Alzheimer’s and heart disease.”
Normally when researchers convert skin cells into iPS cells, the cells rest on a special layer of materials in a petri dish. The layer includes “feeder” cells that provide nutrients required for the iPS cells to grow and reproduce. In this study scientists generated human iPS cell lines by using a method in which the feeder layer secretes a protein called LIF. Yamanaka, who invented this so-called “Kyoto” method, also directs the Center for iPS Cell Research and Application at Kyoto University.
The researchers then analyzed LIF’s importance in the growth of female iPS cells. Female iPS cells contain two copies of the X-chromosome, which is one of two sex chromosomes. While males carry one X and one Y-chromosome, females’ two X-chromosomes could result in a potentially toxic double dose of genes — except for a unique evolutionary mechanism whereby one of the two X’s is silenced in a process known as “X-inactivation.” This process, which occurs early during the development of the embryo, ensures that females, like males, have one functional copy of the X-chromosome in each cell. But exactly how X-inactivation happens is unknown.
To research this, Gladstone scientists generated female iPS cells on feeder layers without LIF and found that one of the X-chromosomes in each iPS cell remained silent. Those iPS cells that grew on a layer of cells with the LIF protein, however, grew with two activated X-chromosomes. Then, by taking a cell from a non-LIF cell layer and transferring it to a LIF-cell layer, the iPS cell’s inactive X-chromosome switched on and became even more like embryonic stem cells. These results are crucial for future studies of how iPS cells grow and mature. And because this iPS technology lets scientists create stem cells from patients with a specific disease, this new finding could lead to a far-superior human model for studying disease and testing new drugs.
“These results will make it possible to readily generate stable, double-active, higher-quality X-chromosome iPS cells, and study the process more closely,” said Gladstone Research Scientist Kiichiro Tomoda, PhD.
We recently posted about Gladstone Institute's progress at converting scar tissue to beating heart muscle.
Adapted from the University of California San Francisco announcement.
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