Featured Research

from universities, journals, and other organizations

Cloning Can Turn Back The Developmental Clock

Date:
November 28, 2000
Source:
Whitehead Institute For Biomedical Research
Summary:
Settling a hotly debated issue in the field of cloning, a team of researchers from the Whitehead Institute and the University of Hawaii has shown that the egg can reset the developmental clock of a female adult cell, first reversing and then faithfully reproducing an early genetic event called X-inactivation.

Settling a hotly debated issue in the field of cloning, a team of researchers from the Whitehead Institute and the University of Hawaii has shown that the egg can reset the developmental clock of a female adult cell, first reversing and then faithfully reproducing an early genetic event called X-inactivation. X-inactivation is a process by which one of two X chromosomes in female embryos is randomly silenced during development.

The findings, published in Friday’s issue of Science, provide the first molecular evidence for the egg’s ability to reprogram an adult cell back to its embryonic state and show for the first time that the process of X-inactivation in clones occurs in a manner similar to that in normal development.

Since Dolly was first cloned, researchers have debated whether she has random X-inactivation as normal females do or the same X chromosome inactivated in all her cells (the X that was inactive in the mammary cell nucleus from which she had been cloned). In this study, scientists from Rudolf Jaenisch’s laboratory at the Whitehead Institute and Ryuzo Yanagimachi’s laboratory at the University of Hawaii used their expertise in cloning mice to answer this question. Their results show that X-inactivation is random in the cells of cloned animals. The egg therefore is able to reprogram the X chromosome of an adult cell to a state that is appropriate for an embryonic one.

"Scientists have suggested that cloning of mammals by nuclear transfer requires reprogramming of the differentiated state of donor cell to an embryonic ground state, but there was no direct molecular evidence for such reprogramming. The process of X-inactivation is an example. It has never been clear whether this process is reversible during cloning," says Jaenisch. Cloning is a very inefficient process, and it is possible that faulty reprogramming contributes to the low success rate. "It will therefore be crucial to determine whether the expression state of other genes of the adult donor cell can be faithfully reset during the cloning process," he says.

X-inactivation is nature’s way of making sure that males and females have equal numbers of X-linked genes, explains Eggan, the first author on the paper. All human embryos inherit 23 pairs of chromosomes: one pair of sex chromosomes and 22 pairs of non-sex, or autosomal, chromosomes. Embryos that inherit an X chromosome from their mother and a Y chromosome from their father develop into males. Embryos that inherit two X chromosomes (one from each parent) develop into females.

At the earliest stages of embryonic development, both X chromosomes are active in female embryos, but just before implantation, one chromosome is chosen for inactivation and silenced. The X-inactivation is random in the embryonic tissue, but in the tissue that ultimately becomes the placenta, the inactivation is thought to happen by a process called imprinting in which the paternal X is marked for inactivation.

All female adult cells therefore have one X chromosome silenced, and the authors wondered whether cloning can reverse it. To do this, they used green fluorescent protein to label a gene on the X chromosome subject to inactivation and followed its course in different lineages of cloned embryos. This allowed them to tell, based on whether the cells were dark or fluorescent green, which X was inactivated and when.

The researchers then created various populations of donor cells with known X-inactivation states (which could be color coded as dark or green donor cells) and used these donor cells to clone new embryos, transferring the nuclei of these cells into enucleated eggs.

When researchers analyzed the results they found that X-inactivation is random in the embryonic lineage of cloned mice. "This random inactivation indicates that the epigenetic marks that distinguish the active and inactive X in adult cells can be removed and re-established on either X during the cloning process, resulting in random X-inactivation in the cloned animal," says Eggan.

In contrast, the epigenetic marks on the active and inactive X in the donor cell are not removed in the early placental tissue of cloned mice and predispose the active X of the donor cell to be active and the inactive X to be inactive. However, just as in normal development, this somatically acquired mark is ignored during early stages of development as both X chromosomes are expressed, says Eggan.

"Our results imply that the epigenetic marks acquired during normal random X inactivation in the embryo are functionally equivalent to the marks acquired during sperm and egg development, as they both can determine which X will be active and which will be inactive in the placenta," says Jaenisch.

"Although the egg reprograms some aspects of X-inactivation, for instance, turning on genes in the silent X chromosome, there clearly are other aspects that the egg ignores, namely the marks that lead to imprinted X-inactivation in the placenta,"says Eggan.

"It is expected that genes on other chromosomes are also reprogrammed to their embryonic state within the egg. If the marks on the genes on the X-chromosome and other chromosomes are faulty in the cell cloned, the egg may not have the ability to fix them, leading perhaps to abnormal development and death of embryos," say Akutsu and Yanagimachi.


Story Source:

The above story is based on materials provided by Whitehead Institute For Biomedical Research. Note: Materials may be edited for content and length.


Cite This Page:

Whitehead Institute For Biomedical Research. "Cloning Can Turn Back The Developmental Clock." ScienceDaily. ScienceDaily, 28 November 2000. <www.sciencedaily.com/releases/2000/11/001128070428.htm>.
Whitehead Institute For Biomedical Research. (2000, November 28). Cloning Can Turn Back The Developmental Clock. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2000/11/001128070428.htm
Whitehead Institute For Biomedical Research. "Cloning Can Turn Back The Developmental Clock." ScienceDaily. www.sciencedaily.com/releases/2000/11/001128070428.htm (accessed August 27, 2014).

Share This




More Plants & Animals News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Firefighters Rescue Puppy Stuck in Tire

Raw: Firefighters Rescue Puppy Stuck in Tire

AP (Aug. 26, 2014) It took Houston firefighters more than an hour to free a puppy who got its head stuck in a tire. (Aug. 26) Video provided by AP
Powered by NewsLook.com
Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Newsy (Aug. 26, 2014) A study published in the journal "Neurology" interviewed more than 19,000 people and found 15 percent suffer from being "sleep drunk." Video provided by Newsy
Powered by NewsLook.com
Great White Shark Spotted Off Massachusetts Coast

Great White Shark Spotted Off Massachusetts Coast

Reuters - US Online Video (Aug. 26, 2014) A great white shark is spotted off the shore at Duxbury beach in Massachusetts forcing beach goers out of the water. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: Elk Wanders Into German Office Building

Raw: Elk Wanders Into German Office Building

AP (Aug. 25, 2014) A young bull elk wandered inside the office building of a company in Dresden, Germany on Monday. The elk became trapped between a wall and glass windows while rescue workers tried to rescue him safely. (Aug. 25) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins