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What Causes iPS Cells to Retain Positional Somatic Memory?

Image credit: Karagiannis et al. 2018 (https://www.jmaj.jp/detail.php?id=10.31662%2Fjmaj.2018-0005)

Jamila Aug 05, 2020
How do iPS cells retain positional somatic memory?

Induced pluripotent stem (iPS) cells were developed from human neural stem cells and then differentiated into mid/hindbrain precursor cells. It was found that these cells did not express any midbrain or hindbrain-related genes but interestingly the cells had retained increased levels of DLX1 (a telencephalic marker). Furthermore, dermal fibroblast-derived iPS cells did not grow and develop as well as telencephalon–derived iPS cells when transplanted into the telencephalon of the mice’s brain. Therefore, this indicates that the growth and development of iPS cells is greatly affected by the origin of the cell and thus transplanting iPS cells in the location where they were derived from, may substantially improve their growth and maturation.

This research suggests that iPS cells retain positional somatic memory. Now the pending question is how and why does this happen?

[1]Hargus, Gunnar, et al. "Origin-dependent neural cell identities in differentiated human iPSCs in vitro and after transplantation into the mouse brain." Cell reports 8.6 (2014): 1697-1703.

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Incomplete epigenetic reprogramming

Darko Savic
Darko Savic Aug 05, 2020
Positional memory retention is likely due to insufficient silencing of lineage-specific genes. incomplete reprogramming leaves the iPS cell lines with some of the epigenetic signatures from source cells. At these loci, DNA hypomethylation and/or transcription-permissive histone modifications are maintained in iPSCs similar to the source cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760008/ These remnant somatic epigenetic signatures can be reset by continued passaging, cross-lineage differentiation followed by serial reprogramming, or chemical inhibition of DNA methylation and histone deacetylation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150836/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148605/

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