Good news!
"... Now an international team of researchers has gone one better: finding a new way of wiping a cell's memory clean so it can be better reprogrammed as a stem cell. ...
The new method, called transient-naive-treatment (TNT) reprogramming, mimics the reset of a cell's epigenome that happens in very early embryonic development, before and after an embryo implants itself in the uterus wall.
In a series of cell experiments, the researchers showed that TNT reprogramming "effectively erases epigenetic memory", particularly in densely packed regions of DNA – but without deleting other important information imprinted on the genome.
As a result, the reprogrammed cells better resembled embryonic-like stem cells in their function and on a molecular level. ..."
"In a groundbreaking study published today in Nature, Australian scientists have resolved a long-standing problem in regenerative medicine. ... the team developed a new method to reprogram human cells to better mimic embryonic stem cells, with significant implications for biomedical and therapeutic uses. ...
“However, a persistent problem with the conventional reprograming process is that iPS [induced pluripotent stem] cells can retain an epigenetic memory of their original somatic state, as well as other epigenetic abnormalities,” ... “This can create functional differences between the iPS cells and the ES cells they’re supposed to imitate, and specialised cells subsequently derived from them, which limits their use,”. ..."
From the abstract:
"Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function. These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory."
Caution: This is a very long article!
In a First, Scientists Fully Wipe a Cell's Memory Before Turning It Into a Stem Cell : ScienceAlertFig. 1: Distinct trajectories of DNA methylation change during human naive and primed reprogramming.
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