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HSCs are responsible for keeping us alive by granting us an eternal supply of blood cells.  (Source: Microscopy Inc.)

Rice University bioengineers Oleg Igoshin (left) and Jatin Narula may have found the switch that tells HSCs when to differentiate and self renew.  (Source: Jeff Fitlow/Rice University)
Master regulator could allow for easy growth direction, organ creation

Scientists are racing towards a future vision in which humans can regrow failing organs and essentially obtain immortality.  Along the way, they're shooting for the more obtainable aim of curing a number of diseases (cancer, Alzheimer's, Parkinson's, and paralysis, to list but a few) using stem cells.

A critical problem though is how to direct stem cells to become the proper tissue type.  Within the human body, there are a rich variety of cells -- endothelial cells, muscle cells, blood cells, osteoblasts (bone), and nerve cells to name but a few.  At some point in the development of the human body, these cell lines were created by a biochemical signal which instructing stem cells to become the particular cell type.

Experimentalists at Cambridge University and Rice bioengineers Oleg Igoshin and Jatin Narula have examined one of these critical biochemical signals.  Based on a computer model developed at Rice and experiments at Cambridge, they believe that a trio of regulatory proteins known as the "Scl-Gata2-Fli1 triad" controls the differentiation of hematopoietic stem cells (HSCs), the self-renewing cells the body uses to make new blood cells.

In healthy adult humans, each day HSCs are responsible for the creation of 100 billion new white and red blood cells.  HSCs are also capable of "self-renewing" if the bone marrow is damaged.

The research at Rice delved into looking at the three regulatory proteins and developing an mathematical model for how they interacted with HSCs.  In their model, the proteins act as a bistable switch, with two states -- "replenish HSC" and "differentiate".  The system ignores extraneous signals and throws the switch only when a signal persisted.

Igoshin, an assistant professor in bioengineering at Rice, comments, "We don't yet have the experimental verification that this is the master-level regulator for HSCs, but based on our model, we can say that it has all the properties that we would expect to find in a master-level regulator."

Jatin Narula, a Rice graduate student, adds, "In examining the results from the model, we found the triad did have the characteristics of a master regulator.  The first time it's switched on, all the cells stay on. It also handles deactivation in a controlled manner, so that some cells differentiate and get deactivated and others don't. Finally, it has the ability to discern whether or not the level of signal is present only for a short burst or for a significantly long time."

Rice researchers hope that the regulatory triad motif reappears in other types of stem cells, possibly leading to more breakthroughs.

The results of the study are published in the journal 
PLoS Computational Biology.



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In silico biology does not equal real biology
By HeavyB on 5/7/2010 10:22:10 AM , Rating: 1
If it were only that easy....




By troysavary on 5/7/2010 11:43:14 PM , Rating: 4
How about doing some research before shooting your mouth off. Conservatives were never against stem cell research. What they are against is creating embryos for the purpose of harvesting stem cells. Try to look up the difference between adult stem cells, which is what this article is about, and embryonic stem cells.

Every attempt to use embryonic stem cells in therapy has been an abject failure. Not only have they failed to produce any benefit, in many cases they have had rather detrimental effects. On the other hand, adult stem cells, which can be harvested from the person needing the therapy him or herslef, have had many successful applications so far. This is a very promising area, but liberals are so caught up in killing babies, seemingly one of their favorite goals, that they ignore this fact and push for more embryonic research, all the while claiming conservatives are "anti-science".


By eskimospy on 5/8/2010 11:45:03 AM , Rating: 1
Shockingly enough, liberals are not cartoon super villains bent on killing as many babies as possible. If you truly believe what you wrote, you are incapable of looking at this issue rationally as you are blinded by ideology.

The boring and old abortion debate on whether or not an embryo constitutes life or not aside, the argument you present is a false choice. It's not adult vs. embryonic, it's adult vs. adult and embryonic stem cell research combined.

If there end up being no effective treatments to be had through embryonic stem cell research, the funding and the research will dry up on its own, no ban needed. Conservatives aren't trying to ban it based upon the merits of the science though, they are trying to ban it based upon their personal morality. While everyone would likely agree that science should be subject to the limits of morality in some cases, this opposition is by definition anti-science.

Maybe embryonic stem cells will be an abject failure, but if we are presented with a problem and someone tells you 'the solution to this problem is under either box A (adult stem cells) or box B (embryonic stem cells), a smart and rational person looks under both boxes . This is why in poll after poll (depending on methodology) the public support for embryonic stem cell research is anywhere from the mid 50% range all the way up to about 75%. To the best of my knowledge is has NEVER been exceeded by those against embryonic stem cell research.


RE: In silico biology does not equal real biology
By ekv on 5/8/2010 9:14:02 PM , Rating: 2
I think you are blinded by your ideology. The ban on embryonic stem cell research was a ban on federally funded research. Private companies can and did fund embryonic stem cell research. So far, no breakthoughs have been found. I might add, nor are likely to be found, since articles have been published pointing out the instability of embryonic stem cells.

You seem to be going through extreme contortions in order to argue your case. Based on a false premise, you are only going to come up with a false conclusion.

Having certain morals guide your progress does not mean you are "anti-science", but rather that you are indeed a plateau above the animals. Do you have trouble being differentiated from the animals?


By eskimospy on 5/9/2010 6:43:54 PM , Rating: 2
By all means let me know what 'extreme contortions' you think I am going through, along with the 'false premise' that you believe my reply was based upon.

Methinks you are projecting some, big guy. :)


RE: In silico biology does not equal real biology
By ekv on 5/10/2010 1:08:51 AM , Rating: 2
I guess I don't understand. It's rather plain English. Perhaps you're incapable of doing an Internet search? or are you just lazy? Try "Stem Cell Controversy"

Even a liberal web-site says
quote:
The current Congressional ban on federal funding for human embryo research allows stem cell researchers to work with only existing stem cell lines.
That was 2006. Obama has undone this, just for the sake of undoing it I'd wager, the typical liberal knee-jerk reaction. How naive can you get.


RE: In silico biology does not equal real biology
By eskimospy on 5/10/2010 9:27:23 AM , Rating: 2
Yeap, that's what I thought.

Bush's funding for 19 lines was woefully inadequate and anyone who has spent more than 5 minutes reading about this subject knows it.

Furthermore, since my post wasn't based upon Bush's policies but instead the merits of an open approach that conservatives generally oppose, the fact that you thought you were undercutting me by posting it shows how poorly you understood what you read.

I can already tell you're just here to fight,not to actually discuss it. Grow up.


By ekv on 5/11/2010 12:36:50 PM , Rating: 2
Excuse me? What are you thinking?!

Bush's funding ought to have been zero. I have moral reservations about Federal funding of a questionable scientific endeavor / fishing-expedition. I'll say it again, private companies can and did continue their research. It's their money and, while we're less free than a couple years ago, it's still a free country.

Yes, I'm here to fight. What was your first clue?


RE: In silico biology does not equal real biology
By ekv on 5/7/2010 3:55:04 PM , Rating: 2
Do you remember what ultimately happened to the tobacco industry?

AGW demagogues and their supporters are engaged in a religion. Anybody who denies the faith is scourged, excoriated and excommunicated.

Please read
http://www.financialpost.com/opinion/story.html?id...

http://www.financialpost.com/opinion/story.html?id...

You'll have to search the page for the Lord Oxburgh's comment [rather unbecoming for a person of his station, no?]

http://www.indymedia.org.uk/en/2005/02/305418.html

http://www.thegwpf.org/climategate/705-lord-oxburg...


By pepito perez on 5/7/2010 4:46:21 PM , Rating: 2
In fairness I don't care about the extremist in either side. You will find fanatics everywhere. What really concerns me is when a significant number of educated and intelligent people choose to question the scientific community and method over an specific topic.

No, global warming is NOT a fabrication. As with any other scientific conclusion there is an error margin and in this case might be bigger due to the magnitude and complexity of the subject. So let's say that instead of 90% of screwing the planet, there is "just" a 50% or even a 30% probability (whoever thinks is 0% qualifies for homo but not for sapiens). Let me ask you: With how many bullets would you be willing to play Russian roulette?

Do people doubt of the scientific community and the scientific method when they switch on their computer, take a plain, open Google Earth? I wonder then why some people feel free to challenge that same scientific community and scientific method when it comes to evolution, global warming, the holocaust or any other subject they choose they don't like.


By ekv on 5/8/2010 3:28:19 AM , Rating: 2
Thanks for nothing. You clearly did not read the ref's posted.
quote:
Global warming alarmists relentlessly chant that there is scientific "consensus" that the "science is settled." Yet now we are told that somehow the main body for promoting the climate change agenda "neglected" to tell the world that the science wasn't settled.
The scientific method, for your information, involves advancing a theory based on repeatable observation. Other scientists then examine said theory, attempt to duplicate the results and either shoot down the theory or support it.

Telling me the science is settled when it isn't ... is just a lie. I can pull statistics out of my head just like anybody else. But then read what Disraeli wrote "There are three kinds of lies: lies, damned lies and statistics." If I believed like Chicken Little that the sky is falling then I'd be trying to make decisions based on a false dilemma. Similarly for your Russian roulette.

Your last paragraph is absolutely opaque and undecipherable, i.e. it does not make any sense. In general, just like AGW proponents.


By ekv on 5/8/2010 2:56:59 AM , Rating: 2
how quaint, argument by Wikipedia...


Stem Cells are not the answer to immortality
By sleepeeg3 on 5/7/2010 8:11:42 PM , Rating: 2
Despite the author's claims, stem cell research will never allow us to live indefinitely. Stem cells age, just like normal cells so even if we discover the ability to direct them into crafting entirely new organs, the organs they replace will be the same age as the rest of your body. This has to do with the shortening of telomeres and the loss of cells ability to protect their DNA, leading to mutations like cancer. Essentially, you could keep growing new organs to transplant back into your body, but if you use your own cells, they will only last approximately as long as the rest of you. This is why the cloned Dolly the sheep aged so quickly.
Here is a brief article on it: http://www.nature.com/nchembio/journal/v3/n10/abs/...

To compare this to a car, it is like turning your brake rotors. Rotors have the top layer scraped off to leave a fresh layer for your brake pads to grab, but eventually, they get too thin to be effective. Replacing them with new parts is the only real fix.

Now if we were to use fetal stem cells, we could generate organs with virtually no accumulated genetic damage, however donors would have to use anti-rejection drugs for the rest of their lives and with 1-100 trillion cells in the human body, this would only save the vital organs - not make us live forever.

If you want the answer to immortality, we have to solve the telomere problem. We have to find a way to activate the telomerase enzyme in our cells to regenerate our cell's protective telomeres, without allowing our cells to run amuck and become cancerous. Once we figure out how to control this, we also have the cure for cancer.

After we solve this, we can look at the other possible causes of genetic damage like oxidation of our mRNA that may be the other reasons for aging.




By dark matter on 5/8/2010 8:34:48 AM , Rating: 2
I don't we will ever be able to prevent ageing. It is such an important part of life that I believe you would have to fundamentally change so much DNA that we would no longer be even human.


By icanhascpu on 5/10/2010 5:44:20 PM , Rating: 2
Aging literally is preventable, its just way out of the reach of humanity right now and for many hundreds of years I would venture to guess. No to mention impractically expensive when we were do discover how to fix the degradation that happens to DNA.

I believe simple slowing of that degradation is going to be the future. We already live on average twice as long as we did a thousand years ago, and that is mainly from medical advances. The huge bottleneck a in human longevity is that degradation. Once that becomes slowed, or even able to regenerate that, mankind will see a huge jump in lifespan.

Saying its a part of life doesn't really mean anything. My computer crashing sometimes is a part of Windows too, but that doesn't stop MS from trying to improve the stability.

Saying they may not even be human from that is silly. Can they still breed with another human? Then they are human. Less syfy channel bro.


RE: Stem Cells are not the answer to immortality
By icanhascpu on 5/10/2010 5:32:47 PM , Rating: 2
So why not at birth or at some young age where such a procedure is most effective we have our own stem cells harvested to a degree, and frozen for use in the future.

That isn't immortality, and really, no one practical thinks that, but that solves a couple issues you're bringing up.


By icanhascpu on 5/10/2010 5:55:04 PM , Rating: 2
By sleepeeg3 on 5/14/2010 4:49:26 PM , Rating: 2
Storing stem cells at birth might eventually be a possibility, assuming they could be viable 60 years later. It could certainly help us live longer. The problem still remains that the rest of us is still aging (i.e. your skin) and will be more likely to become cancerous.

Genetic engineering at the fertilized egg cell stage will likely be the only way to permanently extend our lives. Finding a drug to turn on telomerase in our cells to continually rebuild our telomeres may be possible, but it is not going to solve the issues that seem likely to crop up with an increased risk of cancer. We also have to solve the problem with mitochondrial DNA damage due to oxidative stress. Can this all be solved with drugs? Maybe. I think the solution is obtainable within 50 years if we make a concerted effort to determine how to overcome these issues. Unfortunately, there are far too few researchers investigating this. I intend to become one of them.

Here is a fairly interesting overview on the subject:
http://nar.oxfordjournals.org/cgi/content/full/35/...

Would changing our DNA still make us human? Of course. Triggering something naturally in our DNA could just as easily have happened through a random mutation. If you want to look at the religious angle, we are using the minds that we were given to overcome inherent problems with our bodies. Do people see it as wrong to use medicine, glasses, sunscreen to overcome these defects or extend our lives? Of course not. This is just another physical limitation to be overcome by mankind.


A fantastic finding
By AzureX120 on 5/9/2010 9:26:23 PM , Rating: 2
Hopefully this will allow them to find other methods of SC differentiation beyond hematopoietic cells. This is a key understanding to all lines of stem cells.
BTW some inaccuracies in this thread. Banning federally-funded labs from using embryonic stem cells is hugely detrimental. It means if you accept ANY federal money for ANY project you can't research using new lines. New things are being found all the time but you can't expect it to be super groundbreaking. Placing bans on lines just slows the process.

Even if the bistability modeled in this paper is wrong, it probably is not terribly inaccurate and could end up pointing people in the right direction following additional experimentation. If it is accurate it could lead to many other differentiation models for other stem cells.

Finally what is up with Dailytech and global warming conspiracy theories? Get a grip people...




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