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Archive by date: July 2009

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More on the stem-cell treatment detentions in Hungary

Doug Sipp of the RIKEN CDB and Kyoto University CiRA offers this additional information on yesterday's post:This recent development is interesting for a number of reasons. One of the people arrested, Yuliy Baltaytis, has been working in stem cell tourism for several years, and gained notoriety when a clinic he operated in Barbados, The Institute of Regenerative Medicine, was closed after a BBC expose made allegations that the fetal stem cells used in treatments were being sourced unethically in the Ukraine. He has also collaborated in the past with William Rader, of Medra fame. The Budapest Times is claiming that the cells being used in the treatment that led to the arrest were human ES cells, but given Dr Baltaytis' history, it seems more likely that the intended cells were indeed of fetal origin.

(Along with colleague Sorapop Kiatpongsan (currently at Harvard), Sipp has written up his analysis of unregulated stem cell clinics for Nature Reports Stem Cells and Science[subscription required])

On a personal note: I interviewed the Barbados Institute for a story I wrote back in 2005 for Nature Biotechnology (sub required). At the time, they were burnishing scientific credentials, but a dip into the archived web revealed that they had previously advertised themselves as a stem cell spa. (Here's an analysis of how unregulated stem cell clinics advertise on the Internet)

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Hungary detains four for illegal stem-cell treatments in private clinic

Hungarian police have detained four people for planning to carry out untested, illegal stem cell treatments, according to Reuters.

It is unclear what diseases were being treated, but one Hungarian, two Ukranians, and an American were detained just as they were about to treat a new patient. The American had reportedly been running the clinic in Hungary since 2007. A Ukranian prepared the stem cell injections, and patients generally paid $25,000.

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Last ISSCR 2009 post: thanks to many and congratulations to the poster winners

This month marked the 7th ISSCR meeting for the society and the third for me, and as always, there was much more news worth covering than bandwidth to do so.

I had some help this year, the result of an experiment asking for volunteer writers to send me summaries of the sessions and posters they found most interesting. These posts (you can find them by searching ISSCR or “conference blogs”) made the coverage this year fuller and wiser. I am very grateful for the contributions of Julie Clark, Andrea Ditadi, and Teisha Rowland. Also, thanks to professor Jeanne Loring for her comments on the write-up of Yamanaka’s talk, showing that iPS cells derived from different cell types behave differently.

If a dark-haired 30-something woman sidled up to you in Barcelona with an onslaught of questions (“What was your favorite session? Did you believe that last talk? Is X an established concept or a new idea?”), that was probably me. Thanks everyone for patiently sharing your knowledge, tips and insights. You literally make my job worth doing.

I also know there is a lot more to do. As we walked out of the last talk on the last day of the conference, I asked the outgoing society president Fiona Watt for some of her clearest memories of the past year. She was cheery at the conclusion of a meeting that she’d felt had gone well (our conversation was continually interrupted by attendees offering her handshakes and congratulations). Still, one of her comments struck me as a growing problem:

“Things obvious to one section of our community are not obvious to others.”

Finally, though I had nothing to do with it, I know several scientists put a lot of time into assessing and picking poster winners. I’m sure you’ll see some of this work in the peer-reviewed literature before too long. In the meantime, here’s a sneak peak.

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p53 at ISSCR: not just for cancer anymore

Most scientists who think about p53 are probably working on cancer rather than pluripotency, but a suite of talks is putting that protein on stem cell biologists’ radar.

At ISSCR, Shinya Yamanaka of Kyoto University presented data showing that both p21 and p53 offer barriers to reprogramming: attempts to reprogram fibroblasts that lack p53 are much, much more efficient. Konrad Hochedlinger at Harvard described similar results. Hochedlinger and others have created iPS cells with inducible versions of pluripotency genes, then used them to generate mice whose cells already contain the genesnecessary for reprogramming; no new viral transfection needed. Shockingly, though, activating these genes in fibroblasts made from these ‘reprogramming-ready’ mice does not yield very efficient reprogramming rates. However, Hochedlinger’s lab found that if p53 is knocked out in these secondary cells, the reprogramming rates soar to over 80%. Hochedlinger has been experimenting with genes associated with senescence (INK4a/ARF) as well as blood cell types at varying stages from senescence. He found that, generally, the further a cell is from the senescent state, (i.e. the more divisions it has left in it) the more efficiently it reprograms.

Jacob Hanna from Rudolf Jaenisch’s lab at the Whitehead presented results adding another insight to these finding. He and his colleagues worked with several passages of blood cells that already contained insertions of pluripotency genes. They found that, given enough time, just about any cell can be converted to pluripotency. Suppressing p53 clearly has the power to boost reprogramming rates, possibly because the knockdown of p53 causes cells to divide twice as fast for reasons likely to be linked to the cell cycle. (But of course, other explanations will be found elsewhere. Hanna, for example, also found that overexpressing Nanog accelerates reprogramming independently of accelerating cell cycle.)

The first publication I’m aware of that linked p53 to the efficiency of induced pluripotency was by Hongkui Deng in Cell Stem Cell in November last year. It’s certainly not going to be the last.

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Round-up of regenerative medicine stories and a big, squeaking accomplishment

Two groups of researchers have at last completed a stringent test to show that induced pluripotent stem cells have the same developmental potential as embryonic stem cells: inserted into a special embryo, they can contribute to all the cells in a new mouse, litters of which have now been produced. (See the Nature news story)

GoogleNews was saturated this morning with stories of how to regenerate the heart:

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Italian court rebuffs stem-cell scientists; Australian Stem Cell Centre restarts

Italian court sidesteps challenge
Three Italian scientists who sued their government over the mysterious insertion of language banning human embryonic stem cell research have been told that individuals cannot challenge funding policy. (For descriptions of the administrative court’s decision see Nature’s News in Brief or ScienceInsider)
See Nature’s news story on the scientists’ decision to sue

Latest Australian stem cell plan revealed

The Australian Stem Cell Centre has not had an easy time, but it’s just announced its plan going forward. According to the Australian newspaper, its board resigned en masse in September last year, shortly after sacking its chief executive officer for favoring commercial activities over more basic research.

The new board was announced this spring.

Now the Centre has announced plans to fund large collaborations with a focus on four areas:
1. Ways to propagate stem cells (i.e. bioreactors and growing surfaces)
2. Ways to make pluripotent stem cells
3. Ways to differentiate pluripotent stem cells
4. Studying adult stem cells and applying insights gleaned from one organ to other organs

The Centre, which was founded in 2002, has been awarded AU$111 in state and federal funding, to be paid in installments over that time.

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Mouse study shows stem cells might help Alzheimer's

Headlines from a recent PNAS study showing that stem cells can reverse dementia in mice keep popping up in my inbox. Here's the press release. The cells don't actually become neurons but instead secrete a well-studied protein called brain-derived neurotrophic factor that stimulates neurons already in the brain to form new connections. The paper from UC Irvine scientists is supposedly out today, but I can't find it on the PNAS site. I'd like to know how much cognitive performance improved. Also, the researchers used mice genetically engineered to have Alzheimer's. That's often the only way to study this, but I'd like to know how well the model represents human disease and also whether te researchers started "treating" the disease pathology long before any clinical signs of the disease became obvious, which would mean the strategy may not work for patients that have had Alzheimer's for any significant time. Still, it's cool, and shows that the high, high bar of getting cells to integrate into highly complex tissue may not always be required. (Actually, human trials in the neurodegenerative horror called Batten's disease are underway with StemCells Inc. The injected fetal neural cells are not supposed to integrate into the brain tissue but to help it destroy a toxin that builds up in diseased patients' brains. It's too early to know efficacy yet, but the latest report was that the cells seemed safe.)

In less sanguine news, an autopsy of three Huntington's patients showed that transplanted neural cells did not survive, and that the transplanted cels degenerated faster than the patients' own neurons. (I'll paste the abstract below). Here is a link to this Open Access article as well as a news story from Nature.

Both studies emphasize that not only are techniques fo making specific cell types necessary, but researchers are also going to have to find ways to keep them alive. Compared to the most common animal models, patients are bigger, more complex, and have funcitoning immune systems. As someone recently said of the failure to cure cystic fibrosis in the two decades since the gene was discovered: "we haven't failed. It's only been twenty years."

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ISSCR 2009 meeting: what’s changed from last year?

I asked that question over and over. Common responses were that discussions of iPS cells were less prominent (except at the poster sessions) and talks about tissue-specific stem cells more so. People I spoke with generally felt there was greater variety in topics and presenters than they’d seen before; though at least one felt there was an over-reliance on “ISSCR’s established speakers.” Several thought the meeting, which at around 3,100 attendees was the biggest yet, was growing too large, making attendance a good way to get an overview of related specialties and network, but not as effective for keeping up in one’s own field. General consensus was that most talks described recently published or accepted work. There was a lot of new content in two very jam-packed poster sessions, together exhibiting well over 1000 posters (the numbers went into the 1750s!)

I can't convey all the conversations I had, but I include snippets from Ruth McKernan, Doug Melton, Allan Spradling, Mahendra Rao below.

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ISSCR sessions from Barrandon and Mikkola: thymus makes skin, SCL starts up HSCs

Note: These accounts of talks given at ISSCR were written by Andrea Ditadi.

Yann Barrandon: Thymus cells make skin, hair follicles

The skin, vagina, cornea, esophagus and other organs in contact with external environment, no matter their germ layer of origin, are all covered with stratified epithelium. Such epithelium is characterized by cells that undergo constant self-renewal. Yann Barrandon of Lausanne University Medical School reported some years ago that this long-term renewal was due to a population of multipotent, clonogenic stem cells. (Claudinot et al 2005, PNAS). These cells persist in niches and proliferate according to environmental cues. In vitro, these stem cells form colonies that can be serially cultured and transplanted. They can also generate all epithelial structures, including the hair follicle and sebaceous gland. Cells from the stratified epithelium of different tissues express a common pattern of genes. The thymic epithelium, which does not come into contact with the external environment, is not as well studied.
Reports that the cell-cycle regulator p63 is required for both stratified and thymic epithelium to develop suggested that they may share a similar progenitor. When Barrandon focused his attention on thymic epithelial cells (TEC), he found a subpopulation of rat TEC (0.1-0.5%) that are clonogenic and can be serially passaged. Those TEC progenitors can be recovered from both embryonic and postnatal thymuses.
In contrast to progenitors in stratified epithelium, cultured clonogenic progenitors generally maintain their “thymus identity” but also express epithelial/hair markers. Barrandon combined epithelial cells from both skin and thymus and transplanted these under the kidney capsules in immunodeficient mice. However, while epithelial progenitors cannot contribute to thymus development, thymic TEC progenitors can form thymus as well as skin and even complex skin structures like hair follicles.
In a serial transplantation experiment, recovered TEC progenitors from secondary recipients retain a thymic “signature” expressing almost all the ordinary thymic genes. All the results Barrandon showed suggest that thymic epithelium may contain a very immature multipotent epithelial progenitor with a broader spectrum of potential than epithelial stem cells. And it can be speculated that thymic and stratified epithelia derive from the same precursor, even though their position and function are totally different. In any case, understanding how the skin forms complex structures could lead to improvements in skin grafts and treatments for other skin diseases.


Session info
Barrandon Yann
Lausanne University Medical School and Ecole Polytechnique Fédérale Lausanne
IMPACT OF MICROENVIRONMENTAL CHANGES ON EPITHELIAL STEM CELL FATE
Plenary 36. Growth Control in Stem Cells and Cancer Plenary V

Getting HSCs started with transcription factor SCL

Gereige Laurraine, a student in Hanna Mikkola’s lab at UCLA brings new light on the function of SCL/Tal1, a well known transcription factor required for hematopoiesis. Though mouse embryos lacking the gene for SCL die 9.5 days postconception for lack of blood cells, SCL appears dispensable thereafter for hematopoietic stem cell (HSC) development and function.

Laurraine first used ES cells to create hemangioblasts, precursors of both hematopoietic and endothelial cells. To discover which genes SCL targets, she performed Chip-on-chip analyses to compare cells that both expressed and lacked the SCL gene. These analyses indicated that SCL plays a dual role: it activates major hematopoietic transcription factors that promote the development and maintenance of HSC, and it represses transcription factors critical for the specification of other mesodermal fates. (More specifically, SCL activates factors including Gata2, C-myb, Fli1, Lyl1, Tel, Gfi1, Sox17, and represses factors including those that promote cardiac lineages [Gata4, Tbx20] as well as mesenchymal lineages [Foxf1a, PDGF-R-alpha].) Analysis of the acetylation and methylation of candidate SCL target genes in the ES-cell derived hemangioblasts confirmed the activation of hematopoietic genes and the repression of alternative mesodermal ones.
Laurraine was able to abolish SCL expression at a later point in development (She used a Cre-lox system tied to the expression of hematopoietic marker vav). She showed that the number of adult HSC (isolated as murine Lin- ckit+ bone marrow cells) was not affected, and that other HSC genes like Lyl1, Gfi1, C-myb were still expressed even in the absence of SCL. Her results confirm that, once hematopoietic specification occurs, the SCL-induced hematopoietic program is stable even without SCL.
In addition, Laurraine suggested that Lyl1, a factor in the same family as SCL, may maintain the hematopoietic program in the absence of SCL. Indeed, contemporary absence of Lyl1 and SCL leads to a complete absence of HSC. In the model she proposes, SCL plays a major role in the emergence of HSC before E10.5, Lyl1 maintains the SCL induced transcriptional program in HSC/progenitors until birth, and both can maintain the cells after birth.

Session info
Gereige Laurraine, UCLA, Los Angeles, CA, USA,
SPECIFICATION AND MAINTENANCE OF THE SCL INDUCED HEMATOPOIETIC STEM CELL FATE
Concurrent 42. Concurrent Session IIB: Stem Cell Fate Choice

These accounts are by Andrea Ditadi, a postdoctoral fellow studying stem cells at Hopital Necker – Enfants Malades in Paris.

Note from Niche editor This post comes as a response to my solicitation in June calling for people to submit their accounts of ISSCR 2009. I’d asked people to describe what most interested them and to disclose any conflicts of interest. I’m very grateful for these volunteers’ help making more information available.

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ISSCR Friday posters: cell-penetrators, differentiators, memory-storers, and more

NOTE: These write-ups of selected ISSCR posters are by Teisha Rowland, a volunteer Niche blogger and student at UC Santa Barbara.

They include the following:
Culturing MSCs in spheres may boost their differentiation capacity (Bray, Schilling, Burdon, Genever)
Small-molecule primer for ESC differentiation (Zhu, Wurdak, Wang, Schultz)
Alternative to iPSCs: sometimes fusion goes faster (Schneider, Zenke, et al)
A silky cell-penetrating protein for producing iPS cells (Park, Park, Park)

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Business round-up: pluripotent products, all-star academics and headlines everywhere

Academic all-stars from the East and West Coasts of the US have united to advise a company with plans to use induced pluripotent stem (iPS) cells to find drugs. The company, created from the merger of Boston-based Perian and San Francisco-based iZumi, will be called iPierian and run by iZumi CEO John Walker from San Francisco.
See account in FierceBiotech and Q&A with John Walker about iZumi’s business plan (subscription to Nature Biotechnology required)

It’s not just the name that’s new:

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ISSCR plenaries: how to repair 1) a salamander leg and 2) a human airway

NOTE: These two write-ups are by Teisha Rowland, a volunteer Niche blogger and student at UC Santa Barbara.

Limb regeneration takes nerve

Proper limb regeneration in the salamander requires the presence and function of nerves, although it is unclear why this is on a molecular level. Recent evidence implicates a newly discovered protein as having a central role in the innervation of regenerating limbs.

At ISSCR in Barcelona, Jeremy Brockes of the University College London reported that in severed salamander limbs the protein n(ewt)AG, or nAG, is key for promoting regeneration. nAG production, in turn, is linked to nerves in severed limbs.

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ISSCR posters: In vitro stem cell culture: are we doing enough to make the cells feel at home?

This account is by Julie Clark, a Field Application Scientist at Stemgent in San Diego.

Some five dozen abstracts published for ISSCR this year included the word “oxygen”. Each highlighted the benefits of low oxygen (0.2-10% O2) for embryonic, hematopoietic, and mesenchymal stem cell culture. Indeed a steady stream of publications describes how hypoxia inducible factors and reactive oxygen species affect stem cell self-renewal and differentiation. This makes scientists wonder what might be missing in standard in vitro culture conditions.

A discussion with Jit Hin Tan from MIT highlighted the need for continuous hypoxia: Oxygen diffuses from the media surface to the attached cell layer, creating an oxygen gradient over a period of 24 hours. Exposure to atmospheric oxygen can undo this gradient within minutes. Kristiina Rajala from the Karolinska Institute found that low oxygen tension prevented spontaneous differentiation, increased proliferation and supported self-renewal of human embryonic stem cells (hESCs). Sandra Varum from the University of Texas described an alternate way to achieve some effects of low oxygen: antimycin A could mimic the enhanced pluripotency effect of hypoxia by inhibiting complex III of the mitochondrial respiratory chain, thereby reducing oxidative phosphorylation.

Diverse labs have thus identified benefits of hypoxia to cell culture. But, getting these benefits comes at a price. The cost of a hypoxic-incubator closed system starts at $70,000 (about 50,000 Euros). Given the success of culture under atmospheric conditions, researchers will have to think hard about whether to replicate in vitro the low-oxygen atmosphere that cells encounter in vivo.

Note from Niche editor This post comes as a result to my solicitation in June calling for people to submit their accounts of ISSCR 2009. I’d asked people to describe what most interested them, not to write about their own or their collaborators’ work, and to disclose any conflicts of interest. I’m very grateful for these volunteers’ help making more information available.

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ISSCR session: Consistent differences in ES and iPS cells

This account is by Teisha Rowland, a student at UC Santa Barbara who uses hESCs and iPSCs. She runs a blog called allthingsstemcell.com

Physiological differences have not been reported between embryonic stem cells and induced pluripotent stem cells, but new work shows consistent gene expression differences between them. One of the biggest questions in the field has been how similar these cells really are. If there are differences, are those due to suboptimal techniques for making iPS cells, or the fact that iPS cells don’t come from an embryo?
At ISSCR in Barcelona, Kathrin Plath of UCLA reported that there are some distinct gene and miRNA expression differences between them. She compared four iPSC lines made using different methods and found that 15 genes that are consistently expressed in these lines have significantly different expression levels in ESCs. In particular, basic cellular processes are down-regulated in iPSCs compared to ESCs, while regulation of genes involved in differentiation is up-regulated. Plath suggests that this may be because the fibroblasts from which the iPSCs are made aren’t sufficiently reprogrammed. Interestingly, late-passage iPSC gene and miRNA expression more closely resemble the ESC profile than the early-passage iPSC does, in Plath’s analysis. Plath hypothesizes that this may be caused by selecting iPS cells that most resemble ESCs over many passages. Ultimately, Plath suggests that iPSCs should be thought of as a different type of pluripotent stem cell, distinct from ESCs.
See also Plath’s recent publication in Cell Stem Cell
Session and write-up info
Speaker: Kathrin Plath
Talk title: Mechanisms of Transcription Factor-Induced Reprogramming
(Thursday, Concurrent Session I, Track A)

Note from Niche editor This post comes as a response to my solicitation in June calling for people to submit their accounts of ISSCR 2009. I’d asked people to describe what most interested them and to disclose any conflicts of interest. I’m very grateful for these volunteers’ help making more information available.

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Why Yamanaka’s new results don’t (necessarily) spell doom for most human iPS cells

The stem cell field needs developmental biologists not just to use iPS cells, but to pick the best ones. As Shinya Yamanaka finished his talk Saturday morning, I literally felt cold. He’d compared dozens of mouse ES cell lines with iPS cell lines generated from mouse embryonic fibroblasts, tail tip fibroblasts (TTFs), hepatocytes, and even a few lines from stomach tissue. The tail-tip fibroblasts were bad news: they resisted differentiation. Even after in vitro differentiation caused the cells to make neurospheres twice, tail tip fibroblasts injected into mouse brains did not persist calmly as brain cells but instead made big, scary teratomas. Other assays came to similar conclusions. Of course, not every line misbehaved, but the TTF lines were much more likely to do so than the others. (You can read more of the results in Nature Biotechnology )

Right now, Yamanaka said, the only certain conclusion from the results is that researchers need better ways to evaluate iPS cells. But the implications are disturbing: mouse non-embryonic fibroblasts behave badly as iPS cells, and most human iPS cells come from adult fibroblasts. Have researchers been making exactly the wrong sort of human iPS cells? Yamanaka said it was too early to draw this conclusion. “Humans don’t have tails,” he said.

It turns out that’s not such a trivial observation. Among the scientists I cornered after the talk was Juan Carlos Izpisua Belmonte, who has shown that keratinocytes make iPS cells more readily than fibroblasts. “Has everyone been making cells from the wrong tissues?” I asked him breathlessly. He was calm. The tail, it turns out, is one of the last structures to form during development. Cells there retain plasticity long after cells elsewhere have specialized. Like Yamanaka said, more work needs to be done.

Much of the insight for what this work should be will come from scientists’ instincts to eliminate variables. All the lines Yamanaka tested were generated independently. The number and places where the extra pluripotency genes inserted themselves could vary greatly. Making iPS lines from “reprogramming ready” mice might help to ascertain whether its the tissue of origin or the luck of insertion that determines cells' behavior.

Other insight, like Belmonte’s, might come from developmental biology. It made a conversation I’d had just the day before with Allan Spradling ring even truer.

But I have no time to write about this right now. Nor can I discuss the barriers to reprogramming that are being identified and knocked down by Konrad Hochedlinger and others, nor the ever more companies springing up around iPS cells. I’ll do it (and more) in airports as I head home to San Francisco. I also have some posts written by young scientists to add. If you’ve got some other ISSCR links or tidbits, please let me know.

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Thursday at ISSCR

Yesterday, I wandered around the poster session asking for favorite talks, and though my sample was only about 10 attendees, a few speakers’ names recurred. Much of this has been published or will soon be.

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Uncertainty surrounding NIH stem cell guidelines

At the ISSCR meeting in Barcelona, Harvard’s Kevin Eggan told reporters he isn’t sure that any human embryonic stem cells are eligible for U.S. federal funding right now. The principles of the just-released US NIH guidelines are clear on what’s fundable; the details are anything but. And until those details are unclear, Eggan and others are worried that some institutions won’t let researchers use resources acquired with federal dollars; another worry is that institutions won’t let awarded NIH grant funds flow to researchers.

Over the upcoming months, a group of to-be-assembled experts must decide what existing ES cell lines will make it onto an NIH registry of lines that can be studied with federal funding. This means, among other things, convincing the experts that the embryos donated for the creation of the lines were obtained with appropriate informed consent, according to accepted criteria at the time. The older forms are not as good, and some institutions’ forms are better than others, that could, perhaps, lead to a backlash against certain lines. (See When the past catches up with the present ) To mitigate this problem, research institutions could proactively move to reconsent as many donors as they can; having such documentation at the ready could help the NIH expert groups move more swiftly.

Additionally, some research may just fall through gaps of bad timing. For instance, lines created after July 7 must follow specific guidelines in the new criteria. That could mean that some embryos already donated for research can’t be used for making lines because some in vitro fertility clinics haven’t yet modified their forms and procedures.

Clearly it is not President Obama’s intention for the NIH to stall human embryonic stem cell research. The NIH has told researchers it will act expeditiously. But the Institutes also cannot be a rubber stamp; the public must be able to trust the NIH to hold researchers to carefully considered criteria. As Eggan said about moving stem-cell technologies from the laboratory into the clinic: “the fastest way is the careful way.” The NIH should act expeditiously, but it should also take the time it needs to assemble the registry rigorously.

In the meantime, individual institutions will be left in an uncomfortable position of deciding what research they will permit. Research institutions understandably shun the possibility of bad publicity. But, in the absence of compelling new reasons, they should be equally committed to standing behind research that has already passed the scrutiny of ethics committees.

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Germ cells, neurogenesis, and more ISSCR's first day

I asked program committee chair Ron McKay for the highlights I should look for over the next few days of the ISSCR. He tactfully declined to mention individuals. Instead he said was particularly proud of the diversity. “There’s no single agenda here,” he said, “no club.”

So, perhaps it’s not too surprising that no clear highlight has emerged yet. At tonight’s reception, I asked everyone I met to summarize his or her favorite talk, and though there have been only ten talks so far, no single one is emerging as most popular. Here’s a summary: (I’m borrowing phrases from people I spoke with.):

Marianne Bronner-Fraser from CalTech said that epigenetics, in particular histone methylation, seems to control the settings within the gene regulatory networks governing neural crest cell development and migration.

Rusty Gage from the Salk Institute said that adult brains may well be genetic mosaics. LINES elements seem to jump preferentially into neuronal genes in neural precursors. It’s not clear why this would be adaptive.

Elena Cattaneo from the University of Milan showed links between BDNF and the huntingtin protein.

Yukiko Gotoh of the University of Tokyo showed that Wnt and Polycomb proteins together function as a sort of time-keeper, so that the way that neural stem cells respond to external cues is regulated in time.

Azim Surani described multiple states of pluripotency in embryonic stem cells, embryonic germ cells, and epiblast cells. He described some of the complex machinery developing germ cells use as they prepare for totipotency (suppressing somatic programs, reactivating the X-chromosome and pluripotency genes).

Paolo Bianco of the Sapienza University of Rome said that mesenchymal stem cells are not all the same. Some express the muscle marker Pax7! Exploring these differences could help show how postnatal progenitors establish themselves in muscle and other tissues.

Elaine Fuchs of Rockefeller University described the exquisite players that balance resting and proliferation in the skin; Haifan Lin of Yale, how a whirl of RNA-RNA-protein interactions of varying stability) regulate gene translation, Nancy Wexler tooks us on her journey to identify the Huntington gene, Etienne Hirsch of INSERM described how, even as dopamine neurons in Parkinson’s models degenerate, other types of cells proliferate.

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Unfinished cathedrals, stem cells, and Barcelona

Yesterday I walked around Gaudi’s beautiful cathedral, Sagrada Familia, still under construction more than a century after it was started. In the vaults and columns, simple patterns and rules are played out in endless variations making beautiful, complex forms. (If you’re reading this blog, you likely thought of organogenesis instead of architecture.) Gaudi invented new techniques to plumb the limits of his craft: for instance, he made inverted models, in which weights hung from the ceiling revealed the load a column could bear.

So, persistence of vision, innovative models, and new applications of old ideas create Barcelona’s most-visited monument. But, if you’re in the right mood, there are parallels to stem cells. And of course, the field is still under construction.

What do stem cells have that Sagridia Familia does not? Epigenetics. I’ve been asking everyone what’s going to be big at this conference, and it’s not just the most common answer I’m getting, it’s practically the ONLY answer. How does a cell highlight its genome to know which genes to use? Can we intervene in this process? The stem cell community is just now learning how to figure this out.

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Surfeit of stem cell stories in Nature and around

I'm at the ISSCR meeting in Barcelona, taking notes on talks and conversations. Writing that up is on the to-do list for tonight. Meanwhile, here's a quick plug for NPG. The 2 July issue of Nature is packed with stem cell content. The two stacks of free copies disappeared from the venue's literature tables before the first set of talks finished. For those of you who didn't arrive early enough, here's what was in that issue, along with a few stories that appeared online since then.

News stories
Sperm-like cells made from human embryonic stem cells
But results are only preliminary, researchers caution.

US stem-cell research expands
Biomedical agency announces new funding policy for cell lines.

Chief scientist quits California stem-cell agency
Departure raises questions over leadership at flagship centre.

Italians sue over stem cells: someone inserted a phrase to exclude human embryonic stem cell work from funding

Letter to the editor
We must reverse the Bush legacy of stem-cell problems
US researchers rely on very few lines; the NIH should consider what diversity is desired

Review by Shinya Yamanaka
Elite and stochastic models for induced pluripotent stem cell generation Can any cell be reprogrammed to pluripotency?

Research papers
miR-145 and miR-143 regulate smooth muscle cell fate and plasticity

Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells
See related Nature Reports story:Gene therapy combined with reprogramming makes disease-free cells

Cells keep a memory of their tissue origin during axolotl limb regeneration
See related Nature Reports story: Regenerating limb tissue may not dedifferentiate

Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
Nature Reports provides a peek into peer review for this paper
A Nature news story on the cells being studied in clinical trials for heart disease

A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells
See a related Nature Reports story: A tale of two LIFs

NatureJobs article
Multiple fates: Despite the economic downturn, US universities are seeking faculty members with stem-cell expertise. That doesn't mean times are easy.

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NIH stem cell guidelines please scientists

The NIH guidelines in effect as of 7 July don’t specify exactly which human embryonic stem cell lines can be studied with federal funding, but researchers are still pleased. Not only will more lines be eligible for funding, now the NIH has said it will make the time-consuming call of whether embryos used to create lines were donated under fundable criteria (appropriate informed consent, creation for reproductive purposes, donated without financial inducements.) That’s a huge relief for ethics committees at individual universities that might otherwise do redundant, difficult work.

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