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Scientists discover rejuvenation factors in eggs.

SINGAPORE, August 12, 2015 -- Scientists here have discovered metabolic rejuvenation factors in eggs.

The finding furthers understanding of how cellular metabolism changes during aging, and during rejuvenation after egg fertilization.

When a sperm fertilizes an egg, two adult cells combine to form a new embryo. A similar process of combining an egg's cytoplasm with an adult cell nucleus led to the cloning of Dolly the sheep.

However, the metabolic factors underlying this process had remained unclear.

A new study suggests that old mitochondria--the oxygen-consuming metabolic engines in cells--are roadblocks to cellular rejuvenation.

By tuning up a gene called Tcl1, which is highly abundant in eggs, researchers were able to suppress old mitochondria to enhance a process known as somatic reprogramming, which turn adult cells into embryonic-like stem cells.

Researchers found that Tcl1 does its job by suppressing mitochondrial polynucleotide phosphorylase, thereby inhibiting mitochondrial growth and metabolism.

Stem cell researchers had known that egg (or oocyte) cytoplasm contains some special unknown factors that can reprogram adult cells into embryonic-like stem cells, either during egg-sperm fertilization or during artificial cloning procedures like those that created Dolly the sheep.

Induced pluripotent stem cell (iPSC) reprogramming replaces the ethically controversial oocyte-based reprogramming technique.

But oocyte-based reprogramming is still deemed superior in complete cellular reprogramming efficiency.

To address this shortfall, the Genome Institute of Singapore (GIS) team combined oocyte factors with the iPSC reprogramming system. The bioinformatics-driven screening efforts led to two genes: Tcl1 and its cousin Tcl1b1. After a deeper investigation, the team found that the Tcl1 genes were acting via the mitochondrial enzyme, PnPase.

Until then, nobody would have thought that the key to the oocyte's reprogramming powers would be a mitochondrial enzyme.

The stem cell field's conventional wisdom suggested that it should have been some other signaling genes instead.

Tcl1 is a cytoplasmic protein that binds to the mitochondrial enzyme PnPase. By locking PnPase in the cytoplasm, Tcl1 prevents PnPase from entering mitochondria, thereby suppressing its ability to promote mitochondrial growth and metabolism.

Thus, an increase in Tcl1 suppresses old mitochondria's growth and metabolism in adult cells, to enhance the somatic reprogramming of adult cells into embryonic-like stem cells.

The discovery could boost efficacy of the alternative, non-oocyte-based iPSC techniques for stem cell banking, organ and tissue regeneration, as well as further understanding of how cellular metabolism rejuvenates after eggsperm fertilization.

This could help address both the aging and the fertility problems of modern societies.

Citation: Swea-Ling Khaw et al., "Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming," Cell Reports, 2015; DOI: 10.1016/j.celrep.2015.07.032

Abstract: http://dx.doi.org/10.1016/j.celrep.2015.07.032

Contact: Ng Shyh-Chang, ngsc1@gis.a-star.edu.sg

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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:Aug 16, 2015
Words:452
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