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Minority report: Feared iPS-cell "genetic instability" may instead reflect fact that you're a walking mosaic

Minority report: Feared iPS-cell "genetic instability" may instead reflect fact that you're a walking mosaic

Induced pluripotent stem cells, or iPS cells for short – the embryonic-stem-cell lookalikes whose discovery a few years ago won this year’s Nobel Prize in medicine – are not as genetically unstable as was thought. That’s good news for researchers hoping to use the cells to study disease or, someday, for regenerative medicine. But it raises the question of whether and to what extent we humans are really walking mosaics whose constituent cells differ genetically from one to the next in possibly significant respects, says Stanford neuroscientist and geneticist Alex Urban, PhD.

As I wrote in my release about a new study co-authored by Urban and published online yesterday in Nature:

It’s only a few years ago that human iPS cells became available to researchers. These cells act almost exactly like embryonic stem cells, which can be nudged to differentiate into virtually any of the body’s roughly 200 different cell types. But iPS cells can be derived easily from a person’s skin, alleviating numerous ethical concerns arising from the necessity of obtaining embryonic stem cells from fertilized eggs… At least in principle, iPS cells’ genetic makeup closely reflects that of the individual from whom they were derived. Today, “heart cells” derived from a heart patient’s skin can be produced in a laboratory dish so scientists can learn more about that particular patient’s condition and to screen drugs that might treat it. Tomorrow, perhaps, such cells could be administered to that patient to restore heart health without being perceived as foreign tissue by the patient’s immune system, which would otherwise reject the implanted cells.

However, several studies raised worries regarding iPS cells’ genomic stability. Something – the reprogramming procedure researchers use to convert ordinary adult cells into iPS cells, perhaps, or the culturing techniques employed to keep them alive and thriving afterward? – appeared to be inducing an upswing in these cells’ manifestation of potentially troublesome genetic quirks.

The new study, though, shows that what seemed to be changes in iPS cells’ genetic makeup are, in fact, often accurate reflections of existing but previously undetected genetic variations among the cells comprising our bodies.

As many as 30 percent of our skin cells may bear genomic differences from the “mainstream” cells, Urban concludes. Another study Urban co-authored demonstrated genetic differences among human pancreas, liver and kidney tissue. But his latest study indicates that these differences arise within tissue as well as between them. If they extend into ultra-complex organs such as the brain, Urban thinks, they could play a role in neurodevelopmental disorders such as schizophrenia and autism.

Previously: Nobel Prize-netting iPS-cell discovery was initially a tough sell (for me, anyway), iPS cells match embryonic stem cells in disease-modeling smackdown and Nature summarizes iPS cell challenges
Photo by MastaBaba

One Response to “ Minority report: Feared iPS-cell "genetic instability" may instead reflect fact that you're a walking mosaic ”

  1. Paul Knoepfler Says:

    This is a really important paper. Perhaps epigenomic variability in iPS cells may be more of a concern than genomic variability?

    Paul
    http://www.ipscell.com

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