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ISSCR meeting

Posted by , on 1 July 2010

Almost four thousand people attended the International Society for Stem Cell Research (ISSCR) meeting in San Francisco in June. According to the San Francisco Chronicle, about a quarter of the attendees were from California, but other participants traveled from Australia, Europe, and Asia to attend the meeting. There were far too many talks to summarize the entire event, but Development’s new Reviews Editor, Seema Grewal, and I have selected some of the ones that we thought you might find interesting. Where we found a published paper related to the same topic, we’ve linked to the PubMed abstract, so you can look up more information.

Unfortunately (due to a late flight!) we missed the entire first day of the conference, but if you were there, please let us know what you thought of the talks on that day!

Sometimes the possibilities of stem cell research seem infinite, and the burgeoning field of reprogramming cells suggests that indeed a lot is – at least theoretically – possible: We can take a cell from any tissue, reprogram it to a pluripotent stem cell, and differentiate that into any other tissue. (We can now even bypass the pluripotent state and directly convert cells of one differentiated type into another). But as some of the talks at this meeting show, there is still a lot to be learned.

George Daley showed that induced pluripotent stem cells are not entirely a blank slate. His lab generated human iPS cells from umbilical cord blood and from a newborn’s keratinocytes, and differentiated both batches to the two original cell types. Strikingly, the cells that were originally keratinocytes more efficiently generated keratinocytes than blood cells, and vice versa, indicating that the cells had a memory of their previous state, despite being reprogrammed to iPS cells.

Gordon Keller advocated using knowledge from developmental biology to improve differentiation of stem cells. For example, he found that in generating myocytes from hES and iPS cells, different cell lines require different concentrations of activin and BMP4. This is exactly like embryonic development, he pointed out, where cells are not receiving a constant signal from these agonists, but fluctuating concentrations during development determine which progenitor develops into which cell type.

In a thought-provoking talk, Robert Blelloch described how two opposing families of miRNAs, Let7 and ESSC, could appropriately stabilize the switch between self-renewal and differentiation of stem cells. He also presented work from his lab that demonstrated that deficiencies in miRNA biogenesis do not affect mouse oocyte progression and blastocyst development, suggesting that global suppression of miRNA function may occur during this period of early embryo development.

Other talks illustrated how stem cells can be used to understand organ development. Hans Clevers and Brigid Hogan both showed that starting with just one cell, it’s possible to generate “organoids” in culture. Clevers’ “mini guts”, formed from a single LGR5+ cell, contain all cell types of the intestinal epithelium, and Hogan’s “tracheospheres”, generated from a single tracheal basal cell, start showing the characteristics of distinct basal and luminal cells as early as the 16-cell stage.

David Bilder presented exciting work from his group demonstrating that, in addition to their role during intestinal regeneration, stem cells play a crucial role during nutrient-induced growth of the Drosophila midgut. His group observed that feeding induced increases in both symmetric and asymmetric divisions of stems cells to produce increased pools of both stem cells and differentiated cells, respectively. This change was linked to the production of Dilp3, a Drosophila insulin-like peptide, by adjacent muscle cells, highlighting the critical role of the stem cell niche in regulating the activity of stem cells.

The emerging importance of the stem cell niche was a common theme running throughout the meeting. Erika Matunis described how her group has been studying the influence of epigenetic changes in the Drosophila testis stem cell niche. They have very recently identified NURF (nucleosome remodeling factor) as a positive regulator of the JAK-STAT signaling pathway, which is known to maintain germline stem cells and prevent premature differentiation. These studies highlight that cooperation between epigenetic and genetic mechanisms are important for regulating the stem cell niche.

Stem cell research can also serve to study developmental defects at the molecular level. Kehkooi Kee isolated primordial germ cells from hESC cultures and, using these cells, identified the mechanism by which polycyclic aromatic hydrocarbons (PAHs), an environmental pollutant, affect the germ cell population. PAHs have long been associated with developmental defects, but only through epidemiological studies. Kee was able to pinpoint this developmental defect to the aromatic hydrocarbon receptor pathway, which induced apoptosis in germ cells in response to PAHs.

Elly Tanaka showed remarkable data using the salamander as a model system for studying spinal cord regeneration. They have been inducing injury in the tails of these animals and then watching how various signals can induce resident neural cells to rebuild a fully functional spinal cord. They found that injury induced a very localized reversion of neural cells to a progenitor state. These cells were then able to self-organise and re-start the process of neural tube development.

Closing the meeting, ISSCR president Irving Weissman had some thoughts to share with all the stem cell researchers that were present. He called for more collegiality in peer review. “When you think about that review you’re going to do, look at the big picture”, he advised, and he reminded that obstructing someone else’s career with a scathing review of their manuscript does nothing to advance the field.

I also interviewed Weissman earlier at the conference, about the role of the ISSCR, so you can look forward to that if you want to hear more from him.




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7 thoughts on “ISSCR meeting”

  1. Thank you for the great ISSCR talk coverage, Eva Amsen and Seema Grewal! I very much enjoyed ISSCR this year, and thought I’d chime in with a little talk coverage too (especially of the first day that you were unfortunately unable to attend).

    But first, I’ll give a little background on myself, since I have not posted here before. My name’s Teisha Rowland and I am a PhD graduate student at the University of California in Santa Barbara, where I do research with human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). I am also a science writer and maintain a blog on stem cells called “All Things Stem Cell” (http://www.AllThingsStemCell.com) and I also have a weekly biology column with the Santa Barbara Independent called “Biology Bytes” (http://www.independent.com/bio) (about one third of my articles are on stem cells).

    Before the talks started Wednesday afternoon, ISSCR highlighted their new website for people considering stem cell therapies. Whether you’re considering a therapy or not, their new website, “A Closer Look at Stem Cell Treatments” (http://www.closerlookatstemcells.org), is definitely worth checking out. The importance of using the right language when communicating with the public, and only saying what can actually be done with the current technology, was emphasized.

    Shinya Yamanaka discussed making human iPSCs using the reprogramming factor L-myc instead of c-myc. C-myc (along with Sox-2, Oct-4, and Klf4) was originally used by Yamanaka’s group to reprogram adult cells to become iPSCs (c-myc promotes reprogramming efficiency), but activation of c-myc has also been linked to tumor formation. Consequently, Yamanaka’s group tried reprogramming cells using L-myc instead of c-myc. L-myc is not found in cancers, but has a weaker transfection rate. However, by using L-myc instead of c-myc it was found that more iPSC colonies (and fewer non-iPSC colonies) were created (than with c-myc). Lastly, Yamanaka touched upon the importance of creating large iPSC banks for disease treatments, but that in order to do this researchers must decide on the best cell origins to use and the best reprogramming technique.

    Marius Wernig then gave a talk on a recently published paper by his group on direct reprogramming, a topic that will surely only get more research attention in the future. Wernig’s group took fibroblasts from the tails of mice and directly reprogrammed them into functional neurons (http://www.nature.com/nature/journal/v463/n7284/full/nature08797.html). They initially screened 19 candidate factors and were able to narrow it down to 3 (Ascl1, Brn2, and Myt1l). (Back in February, I actually wrote an article on the amazing topic of direct reprogramming, with coverage of Wernig’s findings – for those of you who are interested, it can be found at http://www.independent.com/news/2010/feb/20/direct-reprogramming/ .)

    K. Lenhard Rudolph gave an interesting talk on stem cells, telomeres, and aging (http://www.springerlink.com/content/k462767001824386/). Stem cell function is known to decline with age, and Rudolph’s group has found this to be a response to telomere dysfunction. He showed that mice with dysfunctional telomeres display premature aging (from studies in knock-out mice) and have impaired tissue regeneration, a function that stem cells play a central role in.

    In his talk, Jamie Thomson suggested a bit of a change in how stem cell researchers think of hESCs and their pluripotency. hESCs are pluripotent (they can ultimately become nearly any cell type), but Thomson explained this is done through a step-wise process; hESCs give rise to some progenitors, which give rise to more mature cell types, which eventually differentiate into the target cell type. Thomson brought up an interesting question — Is this final hESC differentiation step similar to adult/somatic stem cell differentiation, and hESCs are just able to initially become a wider array of progenitors? If this is the case, it’s quite important to understand hESCs’ early lineage choices. This early differentiation time point is still very unclear; as Thomson points out, hESCs can differentiate into trophoblast cells (http://www.nature.com/nbt/journal/v20/n12/abs/nbt761.html), which “makes no sense” (trophoblast cells are from the outer layer of the blastocyst, while hESCs are isolated from the inner cell mass). Thomson suggested that FGF plays a key role in this early differentiation point; high levels of FGF can block trophoblast differentiation, and FGF can also direct hESC differentiation to the primitive streak.

    With growing interest in chromatin remodeling during reprogramming to create iPSCs, Kathrin Plath’s talk was quite timely. Plath explained that pluripotency is related to having two active X chromosomes, and that a somatically silent X chromosome is actually reactivated during reprogramming (http://dev.biologists.org/content/136/4/509.abstract). (Interestingly, the reactivated X chromosome can easily be silenced again due to oxidative stress or just expansion in culture.) So, how is the X chromosome reactivated during reprogramming? Plath’s group found that during reprogramming the normal pluripotency genes are activated, and changes to the chromatin structure occur, all prior to the reactivation of the X chromosome. Consequently, further investigation of changes to chromatin structure during reprogramming should greatly help clarify what it means to be pluripotent.

    Lastly, Grigori N. Enikolopov presented data that help solve the mystery of where neural stem cells disappear to as a person ages. It’s known that the number of hippocampal neural stem cells (and consequently neurogenesis) declines with age, but how or why this happens has been unclear. Enikolopov’s group found that these cells don’t just vanish; they turn into astrocytes. And the stem cells do so through asymmetric visions (unlike other adult stem cells), meaning that once they become “active” they leave no stem cell replacement behind. Consequently, as a person ages Enikolopov’s group found that the number of astrocytes increases as the number of hippocampal neural stem cells decreases, but the total sum of these two cell populations remains the same over time.

    1. Thanks for the update on day one! It’s too bad I missed all that. Seema is currently at yet another conference, the Santa Cruz Developmental Biology Meeting, but I’m sure she’ll be happy to catch up on what we missed as well when she comes back.

      Your comment was caught in moderation, by the way, because it had more than 2 links in it. (It’s a mechanism to avoid spam, but it does delay some non-spam comments that just happen to have lots of links!)

  2. I know this is an old post, but I thought it would be worth bringing up again in light of all the attention the recent paper in Nature (Lister et al.) on the epigenetic differences between iPSC and hESC has been receiving by the media. For reference, here’s a link to the paper:
    http://dx.doi.org/10.1038/nature09798

    What I don’t understand is _why_ this recent paper has received so much attention. There have been papers for a couple years now reporting significant differences between iPSC and hESC, and (as mentioned above) George Daley spoke at ISSCR last year about how his group has significant found differences between iPSC lines. This idea is not a new one and has been around for a while now, and yet the media has latched onto this single paper and news of it has spread like wildfire. “The Scientist” was one of the first to report on it:
    http://www.the-scientist.com/news/display/57971/

    I’m wondering whether this paper is really the breakthrough the media has been making it out to be, or just the straw that broke the iPSCs’ back. I’d love to hear other people’s thoughts on this.

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