There’s always something a bit “off” when you look at aging starlets who’ve had some work done. In the same way, researchers in California and Wisconsin recently found that induced pluripotent stem cells (iPSCs) generated from old somatic cells aren’t quite the same as youthful embryonic stem cells (ESCs)—the epigenetics are “off”.
Sure, iPSCs and ESCs look similar in global analyses. But when the CA/WI team looked at whole-genome, single-base resolution DNA methylomes of several iPSC and ESC cell lines with MethylC-Seq, the differences really jumped out.
Here’s what they found:
- Human iPSC and ESC cell lines had 1175 differentially methylated regions (DMRs).
- About half of the iPSC DMRs resembled their somatic progenitors (memory DMRs), whereas the rest didn’t look like either the parent cell or an ESC (iDMRs).
- A lot of reprogramming errors were at CG islands near genes.
- Some errors that were consistently found in the same location in different iPSC lines may be “hotspots”.
- Some DMRs were located in huge >1 megabase, non-CG regions near centromeres and telomeres, where there’s a lot of H3K9me3.
- Memory DMRs and iDMRs often show up in differentiated versions of the iPSCs, so the errors don’t just go away.
It’s possible that these epigenetic differences could hamper iPSC use in therapies, but the researchers say that knowing about the differences is a good first step toward making better pluripotent cells.
There’s a ton of data to review in this one, so your best bet is to find a cozy couch, grab some java, and head over to Nature, February 2, 2011 for the details.