Cells reprogram in 24 hours

Nature News Service ^ | 19 April 2002 | HELEN PEARSON

[AndrewC]

Cells reprogram in 24 hours Erasing molecular memory of parents could shed light on clones. 19 April 2002 HELEN PEARSON An embryo deletes its parents mark early on. © GettyImages Cells naturally wipe out the mark of their parents in 24 hours, say cloning experts. Exactly how may begin to explain the way that animal clones and stem cells are reprogrammed. Not all genes are born equal. In mammals, some genes are imprinted - cells switch on only the copy inherited from mum or dad, not both. This sex stamp must be erased and rewritten in sperm and egg cells, however, so they are correctly labelled as male or female when they fuse to form the next generation. The deletion occurs in as little as a day, Fumitoshi Ishino of the Tokyo Institute of Technology in Yokohama, Japan, and his team have now shown. Even as an embryo is growing, the cells destined to form its ovaries and testes are scrubbing out established patterns of gene activity1. The finding begins to unravel how cells overwrite their history, explains Azim Surani of the Wellcome/CRC Institute in Cambridge, UK. This is something researchers working on cloning and stem cells long to find out. "Any information we get is bound to be helpful," says Surani. Programming skills Hours after fertilisation sperm and egg overwrite their DNA with instructions for making an embryo - imprints remain intact. Cloned mammals are thought to die early or suffer ill health partly because this reprogramming is incomplete; in clones made from some cell types, imprinting is upset as a result. Some of the cell machinery that erases imprints may also do reprogramming, says Wolf Reik, who studies these phenomena at the Babraham Institute in Cambridge, UK. "I'm sure there are going to be parallels." Once found, the molecules involved might be harnessed to improve the efficiency of cloning. Similarly, adult stem cells might be better persuaded to rewrite their normal instructions and generate unusual cell types. But cloning researcher Rudolf Jaenisch of the Whitehead Institute in Cambridge, Massachusetts, is not convinced that the two processes - removing imprinting and reprogramming - are comparable. He says that cloning shortcuts the natural process. Wipe out Ishino's team believe that, under the right conditions, the imprint on a donor cell's DNA is carried unaffected into the clone. They used this to test when nuclear imprinting is erased in a growing embryo. The group made clones from the cells in mice embryos that give rise to ovary and testes. They took the cells at different stages of embryo development. Cells taken after imprinting had been erased gave rise to clones that died very young, they found. Clones from cells that still had some imprinting lasted longer. Clones that have no parental information do not develop to term Fumitoshi Ishino, Tokyo Institute of Technology, Yokohama, Japan Midway through an embryo's growth, genes lose their sex bias and switch into a default state in a day, the researchers conclude. Chemical gags are removed from genes one by one, to make the activity of both copies equal. The speed suggests that the imprinting pattern is actively wiped out, says Reik, rather than being lost passively over many cell divisions. The experiments also add to growing evidence that embryos cannot survive without correct imprinting. "Clones that have no parental information do not develop to term," says Ishino. Similarly, embryos carrying two copies of either the mother or father's genes cannot survive.
References Lee, J. Erasing genomic impinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development, 129, 1807 - 1817, (2002).

[AndrewC]

It's a computing machine.

[AndrewC]

ping

[Big Bunyip]

This sex stamp must be erased and rewritten in sperm ...

Don't expect to borrow my pen!

[Erasmus]

..is.

[Gladwin]

What is the health of the clones made so far? I think there were sheep, cows, and cats? I must be missing some others, also.

[anymouse]

bump for later.

[Nebullis]

Thanks for the ping!Even as an embryo is growing, the cells destined to form its ovaries and testes are scrubbing out established patterns of gene activity.

Note that parental imprinting continues in all cells except the primordial germ cells where the imprinting pattern is changed according to the sex of the embryo.

Here again, we see the necessity of epigenetic processes for proper expression of the genome.

[AndrewC]

Here again, we see the necessity of epigenetic processes for proper expression of the genome.

I'm lost! That undo command did me in. Where is the change data stored? Is it stored as markers on the DNA saying this routine has been run? What triggers the undo? In fact, Arrggggg!!

Fork and Exec

The fork system call in Unix creates a new process. The new process inherits various properties from its parent (Environmental variables, File descriptors, etc - see the manual page for details). After a successful fork call, two copies of the original code will be running. In the original process (the parent) the return value of fork will be the process ID of the child. In the new child process the return value of fork will be 0. Here's a simple example where the child sleeps for 2 seconds while the parent waits for the child process to exit. Note how the return value of fork is used to control which code is run by the parent and which by the child.

#include <unistd.h> #include <iostream> using namespace std; int main(){ pid_t pid; int status, died; switch(pid=fork()){ case -1: cout << "can't fork\n"; exit(-1); case 0 : sleep(2); // this is the code the child runs exit(3); default: died= wait(&status); // this is the code the parent runs } }

In the following annotated example the parent process queries the child process in more detail, determining whether the child exited normally or not. To make things interesting the parent kills the child process if the latter's PID is odd, so if you run the program a few times expect behaviour to vary.

#include <unistd.h>
#include <signal.h>
#include <iostream>
using namespace std;

int main(){
   pid_t pid;
   int status, died;
   switch(pid=fork()){
   case -1: cout << "can't fork\n";
            exit(-1);
   case 0 : cout << "   I'm the child of PID " << getppid() << ".\n";
            cout << "   My PID is " <<  getpid() << endl;
	    sleep(2);
            exit(3);
   default: cout << "I'm the parent.\n";
            cout << "My PID is " <<  getpid() << endl;
            // kill the child in 50% of runs
            if (pid & 1)
               kill(pid,SIGKILL);
            died= wait(&status);
            if(WIFEXITED(status))
               cout << "The child, pid=" << pid << ", has returned " 
                    << WEXITSTATUS(status) << endl;
            else
 	       cout << "The child process was sent a " 
                    << WTERMSIG(status) << " signal\n";
  }
}

PH's fork all the way down.

[Nebullis]

Fork...

Demethylation is a process (presumably) represented by positional and/or temporal stages of the primordial germ cells. And, prior to that, the cells which are destined to become germ cells do so because of positional and temporal gradients set up by a combination of sperm entry point and oocyte gene expression... fork all the way back to the putative universal common ancestor.

[AndrewC]

Demethylation is a process (presumably) represented by positional and/or temporal stages of the primordial germ cells.

Why should you ever get identical twins?

[Nebullis]

It's a mistake! At early stages the cells are still totipotent, when one or more is separated, it looses the positional effects of it's neighbors to the point that it generates new ones on its own.

[Southack]

"It's a computing machine."

DNA is an AWESOME computing mechanism. The programming of our genes is extraordinarily advanced. Until Man made some comparatively recent breakthroughs, DNA was the only known thing in the universe to store data, process code / data, and replicate.

Not a bad track record for what, the last 4+ Billion years!

[AndrewC]

It's a mistake!

How do Siamese twins fit in then?

[Nebullis]

How do Siamese twins fit in then?

They would represent an incomplete separation of the blastomeres. There are also some other unusual twinning processes.