Changing the speed of DNA replication - a new way to improve the cellular reprogramming efficiency
Reversing injury or disease is a major objective in research towards regenerative medicine. Replacing sick or damaged cells with healthy cells in order to repair damaged tissue is one of the most impactful strategies towards that goal. For that, a most promising approach is cellular reprogramming, whereby one cell type in our body could be converted or ‘reprogrammed’ to another cell type. Research carried out at Helmholtz Munich demonstrates new ways to improve cellular reprogramming efficiency, highlighting new potential ways for cellular repair therapies.
DNA replication is one of the most important biological processes. Throughout the course of our lives, each time that a cell divides an exact copy of its DNA has to be generated so that the resulting daughter cells carry identical genetic material. This is a fundamental principle that enables the faithful inheritance of our genetic material. However, how this process occurs at the beginning of life, after fertilization, and its implications for the mammalian embryo are not fully understood.
A group of researchers led by Maria-Elena Torres-Padilla at Helmholtz Munich investigated how DNA replication occurs in totipotent cells in early embryos. “We discovered something that is very simple, but fundamentally important: DNA replication in totipotent cells is much slower than in any other cell type we studied”, says Tsunetoshi Nakatani, first-author of the study. “This was also true for totipotent-like cells, which we can culture in the petri dish. This led us to ask the question: If we manage to change the speed at which DNA replicates, can we improve the reprogramming of cells into totipotent cells?”
In an outstanding experimental effort, the group of researchers observed indeed that slowing down the DNA replication speed – for example by limiting the substrate that the cells use for DNA synthesis - increases the reprogramming efficiency from several cell types, including stem cells.
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