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Stem cells crossing boundaries

Posted by on May 16th, 2013

drosophila midgut hindgutFor most of us, we don’t all end up settled as adults in the same town where we were born.  The same is true for many cells, including some stem cells in the fruit fly intestine.  A recent paper describes the migration of progenitor cells, some of which will later become stem cells, in the intestine of developing flies, with the help of stunning images of these boundary-crossing cells.

Adult stem cells divide and differentiate to compensate for cell loss or cell injury in adult tissue.  Understanding where these adult stem cells originate during development and how they migrate to their final position in adult tissue is an important question in stem cell biology.  A recent paper in Development describes the migration of Drosophila intestinal stem cells during metamorphosis.  Takashima and colleagues traced the migration of progenitor cells in the intestine—in the midgut, hindgut, and the excretory Malpighian tubules.  A subset of adult midgut progenitors migrates posteriorly to form the adult ureters, and in later pupal stages these progenitors migrate to the Malpighian tubules to give rise to renal stem cells.  These results establish, for the first time, the origin of the renal stem cells in Malpighian tubules.  Conversely, during early pupal development a subset of hindgut progenitor cells migrates anteriorly, with these presumptive stem cells later differentiating into midgut enterocytes.  Takashima and colleagues found that Wingless helps regulate the balance of hindgut progenitors that differentiate into midgut or hindgut enterocytes.  These results show that the boundary between the midgut and hindgut regions is not stable until later in development.  Pluripotent progenitor cells are able to cross this boundary and adopt the fate of their new domain.  In the image above, hindgut progenitor cells (green) are found in the hindgut-midgut boundary (the hindgut proliferation zone, HPZ).  Early in development, hindgut progenitor cells were lineage traced and later show their migration across the HPZ and toward the midgut (lineage traced cells in red).

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.
ResearchBlogging.orgTakashima, S., Paul, M., Aghajanian, P., Younossi-Hartenstein, A., & Hartenstein, V. (2013). Migration of Drosophila intestinal stem cells across organ boundaries Development, 140 (9), 1903-1911 DOI: 10.1242/dev.082933
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Enter the EuroStemCell non-fiction writing competition!

Posted by on May 15th, 2013



graphic_non-fiction_example_simpleSpring has sprung! The sun is out at last (sort of), but that’s not the only great news we’ve got from EuroStemCell: we’ve launched our first ever stem cell non-fiction writing competition.

This is your chance tell a stem cell story with your imaginative science writing, by creating a comic or by writing a poem. And you could win 300 Euros and see your work live on eurostemcell.org.

Judges for the competition include CellStemCell Editor Debbie Sweet and well-known science fiction author Ken McLeod, amongst others.

Go on, give it a go! Full details at http://www.eurostemcell.org/stem-cell-competition

 

In other news from EuroStemCell, there’s lots of new material on our website:

Our latest newsletter fills you in on this and more.

Sign up to receive our monthly e-newsletter at http://www.eurostemcell.org/newsletter. You can also keep in touch by following @eurostemcell on Twitter or liking us on Facebook. Your feedback is always very welcome - via these channels or use our website contact form to get in touch.

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Stem cells image competition: the result

Posted by on April 13th, 2013

The results of the latest image competition, this time featuring five beautiful stem cell images, are in! In what rapidly turned into a two horse race between the corn snake dental organ, and the  mouse hippocampus, it was the confocal image of the adult mouse hippocampus that eventually came out on top.

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Taken by Lulu Xing of the University of Melbourne and titled “The Garden of Memory”, this striking  image will be appearing on a cover of Development in the coming weeks.

Many thanks to all who submitted an image for this competition - especially those who made the Final Five - and to everyone who voted. You’ve definitely proved that stem cells can be just as visually stunning as the tissues, organs and organisms you’re more used to seeing on the cover of the journal!

 
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The hair follicle as a system of stem cell biology

Posted by on April 11th, 2013

hair shaft 2013Monday is tax day for most of us on the American side of the pond.  That ought to cause massive hair loss for many folks, but we have amazing hair follicles that constantly regenerate hair throughout our adult lives (well, at least for those of us without male pattern baldness).  A recent paper in Development helps us understand the hair follicle stem cells involved.

Our hair follicles maintain hair growth throughout our adult lives, and go through different predictable phases of growth (anagen), regression (catagen), and rest (telogen).  Each follicle is a little homeostatic system with adult stem cells that have the ability to self-renew and generate all of the cells required in the hair follicle.  It is not completely understood how all of these mechanisms function together to achieve long-term homeostasis, but a recent paper helps identify the lineage progression of the different cell types in the follicle, and the relationships between them.  Takeda and colleagues identified the marker Hopx in adult hair follicle stem cells.  Lineage-tracing experiments showed that Hopx+ cells give rise to all cell types in the fair follicle.  Takeda and colleagues also identified a novel population of Hopx+ cells in the lower hair bulb of follicles in anagen.  Later in telogen, these newly-identified cells differentiate into the K6+ inner bulge layer in the stem cell niche, where they regulate the quiescence of nearby hair follicle stem cells.  In the image above, Hopx (green) is found in several regions of a hair follicle in anagen.  K6+cells (red) are the innermost cells surrounding the hair follicle shaft.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

ResearchBlogging.orgTakeda, N., Jain, R., LeBoeuf, M., Padmanabhan, A., Wang, Q., Li, L., Lu, M., Millar, S., & Epstein, J. (2013). Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells Development, 140 (8), 1655-1664 DOI: 10.1242/dev.093005
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Stem Cells in Developmental Biology: a debate at the BSDB

Posted by on March 29th, 2013

See below a posting from our website (http://amapress.gen.cam.ac.uk/) on the discussion that took place at the BSDB on whether to change or not the name of the society to include Stem Cell Biology. Some of the people who have read it have encouraged me to post it here to see what people think and I believe is a good idea (to open it up to discussion). In many ways it follows the spirit of Olivier Pourquie’s editorial at the beginning of the year in Development (http://dev.biologists.org/content/139/1/1.full)

With my wishes for a good Easter

Stem Cells in Developmental Biology: a debate at the BSDB

Last week the BSDB (British Society for Developmental Biology) celebrated its annual gathering at Warwick. Always a good place to go for quality developmental biology which is enhanced by the arrangement of holding the meeting together with the BSCB (British Society for Cell Biology): these days there is much cell biology in developmental biology. One of the BSDB sessions focused on Stem Cells and highlighted the clear connection between this area of research and developmental biology, or so it seems to some of us but ……perhaps not all.

The AGM of the BSDB had, for the second year running, a ballot to change the name of the society to include “stem cells’ in its name. Thus, the proposal was to change the name from “British Society of Developmental Biology” to “British Society of Developmental and Stem Cell Biology”. The proposal had been flagged last year and, after a vigorous discussion, was rejected, but by a narrow margin which allowed the subject to be brought up again to the AGM this year, where it was resoundingly rejected. But read on……….

The discussion preceding the vote was heated and highlighted several misconceptions about research in stem cells which, perhaps, represent some reality.

The ones in favour argued, correctly I think (I was and am in favour of the change) that Stem Cell research is part of developmental biology and that while there is much that has to do with medicine, the links between Developmental and Stem Cell Biology are strong and essential for both fields, that Developmental Biology can bring rigour and direction to Stem Cell Biology and that Stem Cell Biology can bring challenges, new ways and possibilities for Developmental Biology. They (we) argued that, after all, Stem Cell biology has always been part of Developmental Biology, albeit somewhat cryptically. Including Stem Cells in the name of the society is an acknowledgement of the times and can have its benefits because there is no denying that Stem Cell Biology is a central and key element of research these days; including it explicitly in the Societie’s agenda would allow the BSDB to have a strong voice in policy, funding and education in these increasingly influential area of research.

The ones against the change argued that Stem Cell Biology is different from Developmental Biology, that it has a clinical slant which would attract a different crowd to the meeting, force different content in sessions and, overall, distract us from the main business: the workings and evolution of embryos and systems. It was suggested that such a change would alienate several established constituencies within the society that would abandon the group. Mpre significantly, that, eventually, with another vote a few years down the line, Developmental Biology would be booted out of the title for the society to become the British Society for Stem Cell Biology.

As far as a I am concerned this was a missed opportunity. While I appreciate many of the points made by the ‘noes’ , I feel that their arguments are based on fear for a future that will always take over no matter what we do and that, in the long term, there will be consequences from not seeing this. We live in an increasingly corporate world in which lobbies are important and, in the context of our business, provide the basis for funding and policy. For the Society of Developmental Biology Society to have an explicit voice in the Stem Cell community is not just an extension of its natural remit and interests, but it is a way to bring some real science into a field that is increasingly interested in applications without having covered the bases. The foundations of Stem Cell Biology lie in Developmental Biology and it is important that developmental biologists have a say on decision making in that important field. Stem Cell Biology is not exactly, as some people claim, a new area of research (developmental biologists have been working with stem cells and their lineages for years) but it is certainly an area that recently has come of age to carve its own intellectual niche like, in many ways, Developmental Biology did in the 1970s (let us not forget that Developmental Biology is an offshoot of Embryology). It was argued that Stem Cells are born with Till and McCulloch (1964 Proc Nat Acad Sci. 51, 29–36). True but what they were looking at is the question of the origin of the blood, a problem in Developmental Biology whether one likes it or not. At certain places, and stem cell research is one of them, boundaries blur. Is genomics and bioinformatics genetics? Yes it is. In my book, Stem Cell Biology is part, and a very important part of Developmental Biology.

But let us move away from the heart of the question (of course the scientific content) and look, briefly, to the context of the discussion. The boundary, as I have said is blurred, and a situation can develop (and in certain places is happening) that some people, funding bodies, society, come to see Developmental Biology through the eyes of an unbridled Stem Cell Biology. After all, is it not organs out of cells that is the goal of stem cell biology? And is it not understanding these processes the goal of Developmental Biology? Then, what is the difference? The answer is simple, Stem Cell Biology wants to do, Developmental Biology wants to understand. It would be a pity not to bring them together. One can see here history trying to repeat itself: throughout the XVIII and XIX century engineers and inventors were making steam engines with little knowledge of physics, and they worked, but it is when the knowledge of thermodynamics is brought into the frameowork of the engineers that the engines become efficient. The same can be said of computing where, again, it is physics that makes the hardware that we have today. The fundamental science will always help the more applied side and needs it. So, much to be gained from Developmental Biology having a say in Stem Cell Biology. But there is a second more difficult question: what will be the consequences of the agenda of stem cells running that of developmental biology?

I can see a marginalization of model organisms and a biasing of the agenda towards applied science, applied in a trial and error way, rather than in the tradition of Science. I might be wrong in the extreme formulation of these concerns but I am certain that some of this will happen.

In the end, my impression was that the ‘noes’ were afraid, afraid of the future without realizing that he future will happen and that by not seeing the trends and joining them, we shall always be left to mercy of those trends, without a voice to influence them. I worry that model systems that have taught us so much about basic biology will slowly be squeezed into corners because we do not have a voice to explain that flies have stem cells, that stem cells are part of the make up of an organism which cannot be understood outside its context, that stem cells are a problem of evolutionary biology, that stem cells are a linguistic twist of linage analysis and lineage analysis has always been a problem of developmental biology, from Roux and Driesch to Garcia Bellido with Till and McCulloch in the middle. Incorporating Stem Cell Biology in the name of the society would have been a way of having a strong voice in a trend that is rapidly gaining momentum.

We shall see what the future harbours. The BSDB is a strong society which represents a vibrant and engaging community so there is no reason why things will change rapidly. However, one thing is clear: there is a need for the voice of developmental biologists to be heard in the Stem Cell community. A mechanism needs to be found for this. It is necessary as much to have a representation to remind that community where their real roots lie and the benefits of listening to the fundamentals of their field. There is a drift which was, unfortunately, at the heart of many of the speeches for the no, that Stem Cell Biology is more clinically that basic research orientated. One can see how this can be construed but, decisions like the one we have taken will increase this gap and foster this misunderstanding. It would be good (it is always good) to take lessons from history. As the interactions between physics and engineering prove, there is much to be gained from the interactions between a field that tries to find practical solutions and one that explain the causes of the problems. Let us hope that the BSDB can find a way to influence some of the directions of Stem Cell biology. For the moment it is as if two twins have been separated; each with their own mind but with shared genetics.


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Stem cells image competition: voting

Posted by on March 14th, 2013

Over the last few weeks, you’ve been submitting your images for the Node and Development’s stem cell cover competition. We received a large number of entries, and you’ve proved to us that stem cells - both in their natural environments and in a dish - can be just as beautiful as the embryos that normally grace our covers. After quite some deliberation, we’ve narrowed down the submissions to a short-list of five.

Now it’s your turn to vote for your favourite. The winning image will appear on a cover of Development, and will also feature on the new stem cell pages we’re developing for the journal’s website.

The poll will close at noon GMT on April 10th.

Here are the Final Five. Click on the image to see a larger version.

1. Immunofluorescence of the corn snake (Panterophis guttatus) dental organ with multiple generations of tooth germs. Sox2 expression (red) indicates putative dental stem cells in the epithelial lamina. DNA is stained with Hoechst (blue).


2. Fractal image of neural rosettes forming after the differentiation of mouse embryonic stem cells to neural stem cells. Cells are stained for Nestin (green) and PSA-NCAM (red).


3. Induced pluripotent stem cell colony surrounded by non-reprogrammed and feeder cells. Mouse embryonic fibroblasts were infected with viruses encoding transcription factors Oct4, Sox2 and Klf4 to reprogram them to pluripotency. A day 14 reprogramming culture was stained for E-CADHERIN (green), NANOG (red) and EZH2 (magenta). Dapi is shown in blue. This procedure can also be applied to human cells. The discovery of somatic cell nuclear reprogramming to pluripotency was awarded the 2012 Nobel Prize for Physiology or Medicine.


4. A rendered image of a primary neuronal stem cell culture in which cells were labeled with different fluorescently labeled proteins that differentiate between stem cells (orange/yellow) and their neuronal ‘offspring’ (blue/ green/ purple).


5. Confocal image of an adult mouse hippocampus, the area of the brain where new memories are formed. Astrocytes (green) were observed around the granule cell layer of the dentate gyrus, as indicated by cell nuclei (red). Some astrocytes were derived from neural precursor cell population (blue).



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Revive Postdoc Program – Permanent Call

Posted by on March 13th, 2013



 The Revive Postdoc program offers up to 3 years fellowships to young scientists in stem cell research.




A PERMANENT CALL for application is open, candidates must be first selected by a Revive host lab prior to apply to the program.

The following Revive research labs are currently seeking for candidates to apply in 2013:




Drosophila Developmental Genetics, CNRS URA2578, Institut Pasteur




Retroviruses and Gene Transfer Unit, INSERM U622, Institut Pasteur





Innate Immunity Unit and Lymphopoiesis Unit, Institut Pasteur





Myology Group, UMR S 787 INSERM, Université Pierre et Marie Curie Paris VI




To apply, please send a CV, a cover letter and when requested, referees’ information to the contact person

Application submission deadlines:

Spring session - application submission deadline: May 1.

Fall session - application submission deadline: October 1.

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Stripes and Stem Cells

Posted by on March 7th, 2013

You didn’t stop developing once you were born (or hatched).  Our infant selves barely resemble ourselves as adults, thankfully, and stem cells play an important role in this continued development.  A recent paper describes the identification of a stem cell niche that generates the melanophores that are responsible for the color patterning in adult zebrafish.

The color patterns that many animal species rely on for natural and sexual selection are generated by differences in melanin synthesis in melanophores.  During embryonic development, melanophores are derived from the neural crest.  In many species, such as zebrafish, the patterning seen in adults is established well after embryonic development—when the neural crest is no longer present.  A recent paper in Development describes the identification of melanophore stem cells that are inactive in the larval stages of zebrafish development, and later activated in juvenile zebrafish.  Dooley and colleagues found that the dorsal root ganglia serve as niches for these melanophore stem cells.  The melanophore stem cells are established early in embryonic development, and later spread out segmentally to produce the stripes seen on adult zebrafish.  These cells depend on the protein ErB for neural crest migration and the gene kit ligand (kitlga) to function as stem cells.  In the images above, recovering larval melanophores (green, arrowhead) migrate away from the position of the dorsal root ganglion (asterisk), along the spinal nerves, after morpholino knockdown of the transcription factor mitfa successfully depleted the existing larval melanophores.  The blue arrowhead points to a cell that later migrates.  This pattern resembles the proximity of melanophores to spinal nerves seen in wild-type juvenile zebrafish.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.
ResearchBlogging.orgDooley, C., Mongera, A., Walderich, B., & Nusslein-Volhard, C. (2013). On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish Development, 140 (5), 1003-1013 DOI: 10.1242/dev.087007
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Image competition: stem cells

Posted by on February 20th, 2013

In a journal like Development, full of beautiful immunofluorescence images of developing tissues and organisms, it’s quite rare that a picture of stem cells stands out from an aesthetic point of view. Cells growing in a dish just aren’t quite as pretty as multicolour embryos or organs. At least, that’s the impression that we get when looking through the images submitted to the journal as potential cover pictures. But Erin’s posts here on the Node have shown us that pictures of stem cells can be both beautiful and informative, and now we want to give you the chance to prove that a stem cell can be just as eye-catching as a developing pancreas or fly eye.

Do you have a picture of stem cells (either growing in culture, or in their native environment) that you’re particularly proud of? If so, we want to hear from you! Email your picture to thenode@biologists.com before March 13th to be in with a chance of winning our image competition. Shortlisted images will be posted on the Node for a public vote, and the winner will grace the cover of a future issue of Development, and will be featured on the stem cell pages we’re currently developing for the journal’s website.

For more information, see our competition rules and our terms and conditions
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Stem cell decisions and the cell cycle

Posted by on February 15th, 2013

A lot of things cycle in life, even down to the cellular level.  In the developing central nervous system, regulators of the cell cycle play important roles in maintaining the balance between stem cell self-renewal and differentiation.  A recent paper in the journal Development describes a cell cycle regulator in stem and progenitor cells in the nervous system.

The developing central nervous system depends on the divisions of neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs).  In early development, NSCs continuously self-renew in the ventricular zones of the early neuroectoderm.  After neuroectoderm specification, NSCs give rise to NPCs, which divide and differentiate into many different types of neurons.  Proteins that regulate the progression through different phases of the cell cycle have been shown to regulate NSC and NPC divisions, specifically affecting the balance between proliferative and neurogenic cell divisions.  A recent paper in the journal Development identified the role of a zinc-finger transcription factor specificity protein 2 (Sp2) in regulating cell cycle progression in NSCs and NPCs.  Liang and colleagues found Sp2 expression in NSCs and NPCs in the embryonic and postnatal CNS.  Conditional Sp2-null mice had mitosis-arrested NSCs and NPCs in vivo.  In addition, conditional deletion of Sp2 caused a decrease in the number of NPCs and neurons in developing and postnatal brains, as seen in the images above.  Compared with normal cerebral cortex tissue in the early mouse embryo (E12.5), Sp2-deleted tissue (bottom) had a reduced number of postmitotic neurons (purple, arrows, left column).  NSCs (green, left column) occupied the entire thickness of the Sp2-null cerebral cortex, whereas NSCs occupy only the ventricular zone (VZ) in control tissue.  In addition, NPCs (green, right column) were less dense in Sp2-null tissue a bit later in development (E14.5), compared with control cerebral cortex.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

ResearchBlogging.org

Liang, H., Xiao, G., Yin, H., Hippenmeyer, S., Horowitz, J., & Ghashghaei, H. (2013). Neural development is dependent on the function of specificity protein 2 in cell cycle progression Development, 140 (3), 552-561 DOI: 10.1242/dev.085621

 
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