Is conventional reprogramming too… conventional?

Transient naive reprogramming is capable of epigenetically correcting human induced pluripotent stem cells – should it be the preferred method?

Somatic cell reprogramming is a way to reset the genetic instructions in a cell, making it more flexible like a stem cell. This is done using techniques like cell fusion or adding specific proteins called Yamanaka factors.

The goal is to create cells called induced pluripotent stem cells (hiPS cells), which can potentially be used for various medical purposes. However, there are differences between hiPS cells and natural embryonic stem cells, making hiPS cells less predictable in their behavior.

The differences are due to chemical tags on DNA and proteins (epigenetic changes) that get carried over during the reprogramming process. These variations make it challenging to use hiPS cells reliably for therapies, drug testing, and disease studies.

Some studies suggest that a different reprogramming method, called somatic cell nuclear transfer (SCNT), may result in cells with fewer of these leftover tags, making them potentially more suitable for medical applications.

My take on this: In recent research, scientists have been exploring new ways to reprogram cells into a more "naive" pluripotent state, which could be a more accurate model for studying how cells change during development. This could help address the challenges associated with using hiPS cells in various applications.

In a recent study published in Nature, scientists delved into the fascinating world of epigenetics to understand how cells undergo changes in their programming. They were particularly interested in two types of reprogramming: "primed" and "naive."

The researchers discovered that during primed reprogramming, the most significant changes in CG DNA methylation happened between days 13 and 21. In contrast, for naive reprogramming, these changes occurred earlier, before day 13. Additionally, global CA methylation increased within the first 5 days in naive reprogramming and after day 13 in primed reprogramming.

When looking at the specific locations of DNA methylation changes, the team found that CG DNA methylation changed gradually at regulatory elements in primed reprogramming, while naive reprogramming showed only one major change. Furthermore, elements that experienced increased methylation during reprogramming were notably enriched with FOS, JUN, and AP-1 motifs.

In simpler terms, the study uncovered the timing and patterns of chemical modifications in DNA during cellular reprogramming, shedding light on the intricate processes that govern how cells transform and adapt.

Explore this research study on somatic cell reprogramming in greater detail right HERE.

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