October 20, 2020

The Niche

Knoepfler lab stem cell blog

Devil in the details: small oncogenic lesions in iPS cells & ESC

Jeanne Loring, oncogenic mutations in cells
Jeanne Loring.

Yesterday I wrote about how difficult it is to tell different cell lines apart, including normal stem cells and cancer stem cells, especially since some accumulate accumulate oncogenic mutations that may make them seem more similar.

A new paper is coming out that makes this case on a genomic level.

Tomorrow’s Cell Stem Cell edition includes a paper by a team of researchers led by Jeanne Loring that has identified relatively small genomic abnormalities in ESC and iPS cells. While both ESC and iPS cells share a subset of these genomic changes, iPS cells had a particularly high rate of changes.

Two factors make these genomic changes particularly worrisome. First, they are undetectable by conventional karyotyping. Thus, they are relatively difficult to routinely detect by the hundreds of labs working on highly pluripotent stem cells. Second, pretty much all the changes make cells more likely to cause cancer and would be of serious concern in terms of potential clinic use.

The changes included duplications involving pluripotency and cancer-causing genes as well as deletions of tumor suppressor genes, making for an especially cancerous one-two punch.

Loring’s team points out the critical importance of producing iPS cells and perhaps also deriving hESC under conditions that promote genomic integrity. However, a key open question is whether that is even possible as perhaps genomic instability such as duplications of pluripotency genes and deletions of tumor suppressors makes iPS cell formation dramatically more efficient. They could also make hESC easier to establish from blastocysts and grow longer term.

A key second point that Loring makes is that as a field we need to be more aware of these changes and ideally monitor cells for such changes.

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