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Some stem cells hold on to their past, researchers say
Los Angeles Times ^ | February 3, 2011 | Eryn Brown, Los Angeles Times

Posted on 02/03/2011 9:38:37 AM PST by Gondring

Stem cells made from mature cells and rewound to an embryonic-like state retain a distinct "memory" of their past that might limit their potential for therapeutic use, scientists reported Wednesday in the journal Nature.

[...]

They looked at 1.2 billion places in each genome where such chemical markers [epigenomes] exist. The analysis was unusually rigorous — and therefore unusually revealing, Ecker said. Earlier studies examined representative regions in the genome, rather than the whole thing.

[...]

For the most part, the contents of Ecker's metaphorical rooms looked alike. But when they zoomed in, inconsistencies emerged.

In a side-by-side comparison of these induced pluripotent stem cells and embryonic stem cells, researchers from the Salk Institute in San Diego found a consistent pattern of reprogramming errors — places where the iPS cells did not revert completely to an embryonic state.

Large regions of the iPS epigenomes hadn't reverted to the embryonic state, but instead held on to the epigenetic memory of their tissue of origin. When the researchers used the iPS cells to create mature cells in the lab, this memory persisted.

[...]

That does not mean iPS cells can't be used in medicine, experts said. Improvements in technology could one day erase their epigenetic memory.

In addition, Wu said, scientists might find ways to harness that epigenetic memory to help treat disease. For example, if heart cells generated from iPS cells retain some of their cardiac characteristics, he suggested, they might be useful in therapies to treat heart disease.

(Excerpt) Read more at latimes.com ...


TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: epigenetics; epigenomes; ips; ipsc; stemcells
Bad news, but obviously it's just another step in research and not a game-breaker. I haven't read the original paper, but I'm uneducatedly guessing that organ-specific self-donated stem cells wouldn't be hampered.
1 posted on 02/03/2011 9:38:39 AM PST by Gondring
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To: wagglebee

ping


2 posted on 02/03/2011 9:40:36 AM PST by Gondring (Paul Revere would have been flamed as a naysayer troll and told to go back to Boston.)
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To: Gondring
The analysis was unusually rigorous

Didn't read the article ... but when an author makes a statement like this ... the red flags go up.

3 posted on 02/03/2011 9:59:04 AM PST by dartuser ("The difference between genius and stupidity is genius has limits.")
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To: dartuser

I think the excerpt provides the context of that statement. I interpreted it to mean that this is the first time they’ve done a non-sampled approach and looked at the whole thing.


4 posted on 02/03/2011 10:10:46 AM PST by Gondring (Paul Revere would have been flamed as a naysayer troll and told to go back to Boston.)
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To: Gondring; Coleus; Peach; airborne; Asphalt; Dr. Scarpetta; I'm ALL Right!; StAnDeliver; ovrtaxt; ...
stem cell & immunology combined ping

In addition, iPS cells can be custom-made for patients, ensuring a perfect genetic match.

IIRC, this is the first article in the in a general news that made any mention for the desire of a perfect immunologic match.

The regions were clustered near telomeres and centromeres, structures that help direct how chromosomes divide.

Telomerase might help with the telomeres, but the centromeres could need a Nobel prize.

P.S. Epigenetics was my first thought about the difference between these stem cells. I'll try to track down the original abstract, if there is one.

5 posted on 02/03/2011 12:16:47 PM PST by neverdem (Xin loi minh oi)
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To: dartuser
The analysis was unusually rigorous

"They looked at 1.2 billion places in each genome where such chemical markers [epigenomes] exist. The analysis was unusually rigorous — and therefore unusually revealing, Ecker said. Earlier studies examined representative regions in the genome, rather than the whole thing."

IIRC, the last time I checked, there are just a little more than 20,000 genes in the human genome. This is the first time anybody checked for these epigenetic/epigenomic differences, IIRC. They happen as an organism matures after fertilization. That's the reason it's rigorous.

6 posted on 02/03/2011 12:26:07 PM PST by neverdem (Xin loi minh oi)
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To: neverdem
Hmm ... If you can't cast that in x's and y's I have no clue what you're talking about ...

Perhaps I should just defer lol.

7 posted on 02/03/2011 2:16:24 PM PST by dartuser ("The difference between genius and stupidity is genius has limits.")
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To: Gondring; Coleus; Peach; airborne; Asphalt; Dr. Scarpetta; I'm ALL Right!; StAnDeliver; ovrtaxt; ...
Use the link if you want a gander at graphical data that are too small to decifer and supplementary data, EXCEL Files and PDF Files. They want $32 for the article.

Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.

8 posted on 02/03/2011 2:22:28 PM PST by neverdem (Xin loi minh oi)
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To: Gondring

So far, only self-donated cells have shown any value whatsoever. Embrionic stems have had disastrous outcomes across the board, from all that I can recall reading.


9 posted on 02/03/2011 2:23:06 PM PST by editor-surveyor (NOBAMA - 2012)
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To: neverdem
So the fallout is, at first blush, these cells are 'good enough' -- but on closer inspection the cells are not perfect replicas of (so to speak) "real, live, virgin" stem cells, and so they might fail to express certain proteins needed in their final destinations in the same amount or timing as needed, or might produce unwanted proteins, thereby hampering their function?

And this lack of methylation is as far as we can tell, random and therefore not limited to certain genes, which might in principle either be controlled for ("gee, that gene never gets turned on in a liver cell, who cares") ?

BUT such markers -- providing a faint memory of the cells' former role, might make them all the more suited if used to treat / regenerate the same organ from whence they came?

Cheers!

10 posted on 02/03/2011 3:09:55 PM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: neverdem

BTTT


11 posted on 02/03/2011 8:31:29 PM PST by Dr. Scarpetta
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To: editor-surveyor
So far, only self-donated cells have shown any value whatsoever. Embrionic stems have had disastrous outcomes across the board, from all that I can recall reading.

Actually, that's misconception on both points.

Self-donated cell tissue isn't all that's being used for iPSC research. Note University of Texas' successful creation of viable offspring from two fathers (plus an XX blastocyst). Think about it....What a boon adult stem-cell research might be for the gay-marriage movement! We wouldn't have this research if we'd stuck with just embryonic cells, so someday, the gay-marriage crowd might be giving a medal to folks like the scamsters at LifeSiteNews.com for helping Heather to truly have two mommies or daddies!

And embryonic stem cells haven't even had a chance at a human clinical trial yet, considering the first clinical trial patient was started in October 2010, and the second clinical trial (human) was approved in November 2010.

And let's not discount the fact that we couldn't have adult stem-cell successes without the earlier embryonic stem cell work that revealed our current path.

12 posted on 02/03/2011 10:43:08 PM PST by Gondring (Paul Revere would have been flamed as a naysayer troll and told to go back to Boston.)
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To: grey_whiskers

You might find this interesting, too...more sad news...
http://media-newswire.com/release_1138486.html


13 posted on 02/03/2011 10:46:57 PM PST by Gondring (Paul Revere would have been flamed as a naysayer troll and told to go back to Boston.)
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To: Gondring
Well, crud.

Thanks for the link.

14 posted on 02/04/2011 5:52:09 PM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: decimon; martin_fierro; AdmSmith; AnonymousConservative; Berosus; bigheadfred; Bockscar; ColdOne; ..
Note: this topic is from 2/03/2011.
Thanks Gondring. The rest of the epigenetics keyword:
15 posted on 12/11/2011 8:12:10 AM PST by SunkenCiv (It's never a bad time to FReep this link -- https://secure.freerepublic.com/donate/)
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