Many congratulations to Nathan Kenny (University of Oxford), Kathryn McClelland (Institute for Molecular Bioscience, University of Queensland), and Sophie Miller (University of Cambridge), who took this image at last year’s Woods Hole Embryology course. The image shows a squid (Loligo pealeii) embryo stained with anti-acetylated tubulin (red), anti-sorotonin (green), and DAPI (blue,nuclei).
The runners-up to this competition were the annelid larvae by Poulomi Ray (Clemson University), the live squid embryo by Brijesh Kumar (Indian Institute of Technology, Kanpur) and the squid eye by Ezgi Kunttas (Carnegie Mellon University).
The winning squid embryo image will feature in the cover of a coming issue of Development. This was only the first round though, so expect another set of beautiful images from the Woods Hole embryology course here on the Node very soon!
June 1st, 2014: Exactly one year after my departure flight from Bologna to Boston to attend the 2013 MBL Embryology course held at the Marine Biological Laboratory in Woods Hole, MA (https://thenode.biologists.com/six-weeks-in-woods-hole/events/), I was again in the Bologna airport, only that this time I was landing from the States.
I was returning to my home institution, the University of Modena and Reggio Emilia, Italy where I am a last year graduate student, from the Stowers Institute for Medical Research in Kansas City (MO, USA), where I spent the last 3 months working in the laborartory of Prof. Alejandro Sánchez Alvarado.
Thanks to the 2013 MBL Embryology course, where I met Prof. Sánchez Alvarado (Director of the course together with Prof. Richard Behringer), and thanks to the Development Travelling Fellowship, I could collaborate with a great research group in one of the best places anywhere in the world that a biologist can work at: the Stowers Insitute (http://www.stowers.org/stowers-report/fall-2013/best-places-to-work).
At the time of the 2013 MBL Embryology course, I was working mainly on the immune functions of the freshwater gastropod, Pomacea canaliculata, a mollusk which is considered a dangerous pest already invading North America and South-East Asia from the South America. Pomacea is also the intermediate host of the nematode Angiostrongylus cantonensis, which causes eosinophilic meningitis in humans. This snail is aggressively invading new territories because of its adaptability to different kinds of environmental conditions and resistance to multiple stress conditions. As such, the characterization of the immune system of this snail is important for controlling its diffusion by allowing to uncover features that may be vulnerable to intervetions for eradication.
However, after the 2013 MBL Embryology course in Woods Hole, I became highly interested in regeneration and the incredible mechanisms able to activate either stem or differentiated cells in order to increase the proliferative rate and build either amputated parts or whole organisms altogether. More than two hundred years ago, Lazzaro Spallanzani’s experiments (in part performed in Modena, by the way) showed that terrestrial snails are able to regenerate their heads after decapitation. In Woods Hole, I was really impressed by the regenerative capacity of planarians, which can be included with mollusks and other groups into the lophotrocozoan taxon. Because of this, when I returned to Modena in 2013, I tried and cut the sensory organs of P. canaliculata in order to verify if it is able to regenerate.
I was very excited when I observed that after 2, 3 and 4 weeks, respectively, the cephalic and oral tentacles, as well as the eyes were completely regenerated. This observation formed the basis for my period in Kansas City as a visiting student.
Before I left for Kansas City, I collected the samples of the regenerating cephalic tentacles, oral tentacles and eyes of Pomacea canaliculata at different time points. Once at the Stowers Institute, the RNA purification and sequencing of the samples and the bioinformatic analysis of the data allowed for the construction of a transcriptome database. A high-resolution time-course was produced for each organ and the analysis of the gene expression profiles uncovered a significant number of genes differentially expressed during the regeneration processes surveyed. The availability of the transciptome of these complex organs will allow for detailed molecular analyses of the pathways involved in regeneration, providing a solid foundation for my future studies.
These three months at the Stowers Institute, which directly stemmed from the 2013 MBL Embryology course, gave me the chance to write a personal three-month project, learn new techniques, work with a planarian model, perform experiments in the field of regeneration, and collect data that will be surely useful in my future studies. Last but not least, at the Stowers Institute I met a lot of great scientists, and attended many interesting lectures. Equally enjoyable were my interactions with post-docs from all over the world from whom I benefited extensively through their continuous and kind assistance in my lab activities.
I am confident that this experience will reveal of fundamental importance for me and my scientific career.
Cells move in (still) mysterious ways to achieve morphogenesis.
Prominently, cells of an early vertebrate embryo (blastula, a mass of undifferentiated cells) move extensively during gastrulation to generate the three basic layers of the organism: ectoderm at the surface, endoderm presaging the digestive tube, and the mesoderm in between. At the end of the process, the body plan is clearly visible, its main axes established.
This is perhaps most dramatically illustrated in the extremely large embryos of most amniotes (such as in birds and most mammalians, including the human): they consist of thousands or tens of thousands of cells, arranged in an epithelial disc (epiblast). Gastrulation is achieved through a seemingly fixed structure at the midline, the primitive streak (Figure 1).
Figure 1: Chick embryo at gastrulation. The primitive streak is the darker stricture along the midline.
Here, cells engage in epithelial-to-mesenchymal transitions (EMTs, similar to carcinoma progression [1]) to leave the epiblast and contribute to the inner layers. In the chick embryo – a good representative of most amniotes -, virtually all cells in the embryonic disc have long been observed to be engaged in large displacements, directed mainly toward the primitive streak ([2, 3], Figure 2).
Figure 2. Massive movements across the embryonic epiblast. Left, using transmitted light to observe development prior to streak formation. Right, fluorescent marking of the domain where the primitive streak will form (green) and tracks of other groups of cells (yellow; red indicates the direction of movement).
But how is the primitive streak maintained as a fixed structure in the middle of a field of constantly moving cells? How does it form in the first place? To add to the puzzle, massive cell movements in the epiblast actually start well before gastrulation in the form of counter-rotating whorls, the meeting point of which always correspond to where the primitive streak later forms. Is there a causal relationship?
We have now shown [4] that the primitive streak arises by a chain reaction of EMT events. This is primed by rare EMT events, which occur in the epiblast well before gastrulation. EMTs become highly cooperative through a community effect requiring TGF-b signalling. The gene coding for Nodal, a member of this superfamily, is transcribed early in a small domain on the edge of the blastula, but the activity of the protein is antagonised by signals emanating from an amniote-specific extra-embryonic layer, the hypoblast, which initially lines the epiblast. It is its displacement (and the disinhibition of Nodal activity) that triggers the chain reaction of EMTs and, therefore, the initiation and later the maintenance of the primitive streak.
The Nodal expression domain corresponds to a region in which we previously found cell intercalation to occur, in the plane of the epiblast (green in figure 2, right panel) – this is again regulated by the hypoblast, but positively and via different signals (FGFs, [5]). The intercalation region is initially arranged along the edge of the epiblast and intercalation displaces its cells along one of its radii, before gastrulation. So, one key invention of amniotes is a mechanism to regulate Nodal activity and displace it along the future anterior-posterior axis of the embryo, before it can trigger gastrulation. Interestingly, both intercalation and delaying Nodal-dependent chain reaction of EMTs are regulated by the hypoblast, the characteristic evolutionary acquisition of amniotes.
Two key, local cell behaviours therefore drive primitive streak formation. What about the movements in the rest of the epiblast? We turned to computer simulations and we show that these two components can indeed entrain cells in the entire epithelial sheet to move in the correct pattern, and that the model can also represent the experimental conditions of abrogating or ectopically creating one or two of these components. Local actions can trigger global movements.
A few directions now open, which we now pursue in my new lab in Cambridge. There is now a framework for interpreting experiments at molecular or cellular level and linking them quantitatively to large-scale morphogenesis, and refine both experiments and models in step with each other. Such models hold the key not only for understanding large, regulative embryos (including the human), but also for adequately discerning the common developmental patterns and the true acquisitions / losses during evolution, and the constraints that brought them about. Gastrulation also sets the stage for the development of the nervous system and the elongation of the main body axis; we now hope that we have better tools to continue exploring these key issues.
References
[1] Nieto, M. (2011). The Ins and Outs of the Epithelial to Mesenchymal Transition in Health and Disease Annual Review of Cell and Developmental Biology, 27 (1), 347-376 DOI: 10.1146/annurev-cellbio-092910-154036
[2] Gräper, L. (1929). Die Primitiventwicklung des Hühnchens nach stereokinematographischen Untersuchungen, kontrolliert durch vitale Farbmarkierung und verglichen mit der Entwicklung anderer Wirbeltiere Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 116 (1), 382-429 DOI: 10.1007/BF02145235
[3] Wetzel, R. (1929). Untersuchungen am Hühnchen. Die Entwicklung des Keims während der ersten beiden Bruttage Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 119 (1), 188-321 DOI: 10.1007/BF02111186
[4] Voiculescu, O., Bodenstein, L., Lau, I., & Stern, C. (2014). Local cell interactions and self-amplifying individual cell ingression drive amniote gastrulation eLife, 3 DOI: 10.7554/eLife.01817
[5] Voiculescu, O., Bertocchini, F., Wolpert, L., Keller, R., & Stern, C. (2007). The amniote primitive streak is defined by epithelial cell intercalation before gastrulation Nature, 449 (7165), 1049-1052 DOI: 10.1038/nature06211
If you are doing a PhD (or involved in research in any way), you probably take a lot of humour, procrastination and comfort from PHD comics. The comic strip ‘Piled Higher and Deeper’ has been portraying “life (or the lack thereof) in academia” since 1997, with a cast of characters ranging from a nameless graduate student struggling with his PhD to a postdoc with a knack for stealing free food from seminars.
But in the last few years PHD has become more than just the comics. The creator Jorge Cham, has travelled around the world giving talks about the power of procrastination, and PHD TV is a fantastic collection of interesting videos about different science topics and researchers, mixing real life footage with Jorge’s illustrations. Another exciting project spinning off from PHD comics was the PHD movie. Filmed on location at the California Institute of Technology, and starring real life graduate students and researchers as many of the main characters, this feature length movie brought many of the jokes that we have come to love to the big screen. The project was a huge success and the movie was screened at over 500 universities and research institutes across the world. Eva Amsen (the previous Node community manager) wrote for the Node about it when she attended one of these screenings in London (she also interviewed Jorge for the Node before).
Following the great success of the first movie, the PHD team is now keen on creating a sequel, and they need your help! A Kickstarter campaign has been launched in an attempted to raise the $100K required, and you can show your support by making a donation which will not only make the project possible but also give you access to exclusive rewards!
If you haven’t watched the first instalment and want to know what the movie is all about, you can watch the PHD movie for freefor this month only. To give you a taster, here is the trailer:
Postdoctoral positions are available in the laboratory of Amanda Dickinson to study craniofacial and skin development in Xenopus.
I am looking for highly motivated and tenacious applicants with a passion for developmental biology. Qualifications include a PhD in cellular/molecular or developmental biology and experience with Xenopus or zebrafish is preferred.
There are several projects in the lab which include:
-Vitamin deficiencies and orofacial development
-Epigenetic regulation of palate formation
-The biomechanics of forming a face
-Signaling and cell adhesion during skin development
The laboratory is part of a growing group of developmental biologists in the department of biology at Virginia Commonwealth University, Richmond Virginia. Check out these links to learn more about some of the great things about living in Richmond, VA.
Please send a letter of application (including a brief description of previous research experience), CV, and the name and contact information of 3 references to Amanda Dickinson at ajdickinson@vcu.edu.
– How good is a ‘use it or loose it’ model at explaining neuronal connections in the vertebrate retina? The students of the developmental neurobiology seminar at Reed College posted their last journal club discussion.
– And we reposted an article from the F1000Research blog about a recent study where Kenneth Lee and colleagues attempted to reproduce the STAP study.
Outreach:
– Interested in making your own outreach videos? Lilian came across an easy-to-use app that can help you make simple and effective videos using images and sound.
– Our popular Woods Hole cover competition is back! Which image from last year’s course would you like to see in the cover of Development?
– Switzerland is not just about cheese and chocolate- Monika visited the Mosimann lab in Zurich to learn how to use the zebrafish tamoxifen-controlled Cre/lox system.
A postdoctoral fellowship for 3 years is available from October 2014 in Delphine DUPREZ’s team, located in the Developmental Biology laboratory in Paris (bio–dev.snv.jussieu.fr/). The team focuses on tendon and muscle development using animal models. The objective of the project is to better understand the molecular pathways involved in tendon development. The project will involve the use of the chick embryos and mesenchymal stem cells in 2-dimensional and 3-dimensional culture systems.
DUPREZ – Related references:
Guerquin et al.,(2013). J Clin Invest123, 3564-3576.
Lejard et al., (2011) J. Biol. Chem286(7), 5855-5867.
Wang et al., (2010) Dev Cell, 18, 643-654.
Applicants may be of any nationality and should have obtained the equivalent of a PhD less than 2 years. A background in developmental biology or/and an expertise in the use of mesenchymal stem cells will be an advantage.
Applications should be sent to Delphine DUPREZ to Delphine.duprez@upmc.fr
Applications should comprise the following:
– CV
– Description of previous research experiences, publication list and a personal statement describing research interests and career goals
– List of 3 names of referees including email address and telephone number
Any mammal who celebrated Mother’s Day earlier this month realizes how important mothers are for us and the tight bond between them and their children. Forget clean shirts and packed lunch every day; for us developmental biologists, there is no better reflection of this bond than the extraembryonic membranes that support the growth of the fetus in the uterus. These tissues, among other roles, serve as circulatory, digestive and excretory systems until we develop our own. As a matter of fact, they are so important that they begin to form even before the fetus itself – during the preimplantation period, before the embryo attaches to the uterus (check out the cartoon below). Therefore, the very first decisions cells need to make during a mammal’s life are whether to become part of the extraembryonic lineages (called trophectoderm and primitive endoderm at this stage) or become the foundation of the fetus (the epiblast).
Historically, the first of these decisions (whether or not to become trophectoderm) has received more attention by researchers. However, the second one, whether to become primitive endoderm or the pluripotent, embryonic epiblast, has only been studied in more detail over the last decade or so. A number of molecular markers and the cellular behaviors involved in this process have been described, although no transcription factor has yet been shown to be essential for primitive endoderm specification. In the Hadjantonakis lab, we have recently looked at the role of the main suspect – the GATA family transcription factor GATA6 – and we are publishing the results in the current issue of Developmental Cell [1].
Cartoon and timeline for the main stages of mouse preimplantation development, from the zygote (left) to the blastocyst (right). Cell lineages and their contributions later in development (boxes) are color coded: trophectoderm (green), primitive endoderm (blue), epiblast (red). Inner cell mass (purple). Implantation takes place approximately at day 4.5 of development.
This study is important for two reasons: one biological and the other one technical. As I mentioned earlier, this is the first study to show a transcription factor that is absolutely required for primitive endoderm specification. Gata6 null embryos completely lack primitive endoderm because all cells of the inner cell mass default prematurely to epiblast fate (the future fetus). Although they show no other phenotypic defect, these embryos die upon implantation, presumably because there is no tissue to support the growth of the epiblast. We also show that Gata6 heterozygous null embryos have reduced levels of GATA6 and, as a consequence, show a delay in primitive endoderm specification. Finally, this study clarifies the love triangle formed by GATA6, the pluripotency champion NANOG and the fibroblast growth factor (FGF) signaling pathway. FGF4 (or basic FGF/FGF2) is the instructive signal for primitive endoderm specification among inner cells in the blastocyst; however, as we show for the first time in this paper, GATA6 is necessary for cells to respond to FGF4, consequently downregulate NANOG, and acquire primitive endoderm identity. Our paper not only provides a mechanism for the induction of primitive endoderm fate, but also suggests that the relative levels of GATA6 to NANOG in each cell could tip the balance towards either an extraembryonic or an embryonic fate. How these levels change and how cells can measure them remains to be seen…
Proposed interaction between GATA6, NANOG and the FGF signaling pathway. Dashed lines represent hypothesized regulation, grey lines represent weak effects due to low protein concentrations. From Schrode N, Saiz N, Di Talia S, Hadjantonakis A-K (2014) GATA6 Levels Modulate Primitive Endoderm Cell Fate Choice and Timing in the Mouse Blastocyst. Dev Cell 29: 454–467
Our study is also exciting because of the approach we used to analyze the Gata6 allelic series. For those less familiar with it, the mouse preimplantation embryo is as good a model for (live) imaging and single-cell analysis as it is unfit for biochemistry. It is very small, with few cells, and can develop in vitro, without maternal support, in standard culture conditions. This means we can image and analyze the behavior of every single cell within the embryo using a rather simple experimental setup, making it an ideal model to study mammalian cell differentiation in situ. Despite these features, only recently have there been attempts at quantifying gene expression and doing single cell analyses, partly fueled by the technology that has become available [see references 2-4, or, more recently, 5-7, for examples].
In this work, we have used MINS, a piece of software recently developed in our lab [8] that can segment nuclei in series of confocal images with higher accuracy and lower manual input than any other software we have tried so far – including popular (and powerful) solutions like ImageJ or Imaris. MINS collects spatial coordinates and fluorescence intensity data for every channel on each cell, gives them a unique ID, and generates a data matrix for each embryo. After some manual curation for under/oversegmentation and to remove the occasional outlier (generally dead cells), the data is ready for you to do maths and statistics to your heart’s content. Being biologists, large data matrices send shivers down our spines, so we teamed up with physicist-turned-biologist Stefano Di Talia and, lo and behold, the numbers began to make sense! Furthermore, because MINS also collects positional information, we were able to relate changes in protein levels and cell identity to position within the embryo. To a certain extent, this kind of analysis allows us to bypass Western Blots and study protein expression in individual cells, while preserving positional information, which is lost when cells are disaggregated for gene expression analyses. This study is the first of several from our lab where we will apply this pipeline to three- and four- (time lapse) dimensional datasets to understand better the earliest cell fate decisions in mammalian development. We hope the implementation of this analysis pipeline by other labs will improve it and help generate even higher quality data in future studies. The combination of these advanced algorithms for image analysis with single-cell expression profiling techniques will let researchers study with high resolution the molecular mechanisms controlling cellular processes in situ, in intact tissues or embryos. For further proof that this is becoming a thing, have a look at these recent comments: 9, 10.
If you want to discuss or comment, do it below or you can reach me on twitter
References:
1.Schrode, N., Saiz, N., Di Talia, S., & Hadjantonakis, A. (2014). GATA6 Levels Modulate Primitive Endoderm Cell Fate Choice and Timing in the Mouse Blastocyst Developmental Cell, 29 (4), 454-467 DOI: 10.1016/j.devcel.2014.04.011
2.Kurimoto, K., Yabuta, Y., Ohinata, Y., Ono, Y., Uno, KD., Yamada, R., Ueda, H., & Saitou, M. (2006). An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis Nucleic Acids Research, 34 (5) DOI: 10.1093/nar/gkl050
3.Plusa, B., Piliszek, A., Frankenberg, S., Artus, J., & Hadjantonakis, A. (2008). Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst Development, 135 (18), 3081-3091 DOI: 10.1242/dev.021519
4.Guo, G., Huss, M., Tong, G., Wang, C., Li Sun, L., Clarke, N., & Robson, P. (2010). Resolution of Cell Fate Decisions Revealed by Single-Cell Gene Expression Analysis from Zygote to Blastocyst Developmental Cell, 18 (4), 675-685 DOI: 10.1016/j.devcel.2010.02.012
5.Frum, T., Halbisen, M., Wang, C., Amiri, H., Robson, P., & Ralston, A. (2013). Oct4 Cell-Autonomously Promotes Primitive Endoderm Development in the Mouse Blastocyst Developmental Cell, 25 (6), 610-622 DOI: 10.1016/j.devcel.2013.05.004
6.Le Bin, G., Munoz-Descalzo, S., Kurowski, A., Leitch, H., Lou, X., Mansfield, W., Etienne-Dumeau, C., Grabole, N., Mulas, C., Niwa, H., Hadjantonakis, A., & Nichols, J. (2014). Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst Development, 141 (5), 1001-1010 DOI: 10.1242/dev.096875
7.Ohnishi, Y., Huber, W., Tsumura, A., Kang, M., Xenopoulos, P., Kurimoto, K., Oleś, A., Araúzo-Bravo, M., Saitou, M., Hadjantonakis, A., & Hiiragi, T. (2013). Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages Nature Cell Biology, 16 (1), 27-37 DOI: 10.1038/ncb2881
8.Lou, X., Kang, M., Xenopoulos, P., Muñoz-Descalzo, S., & Hadjantonakis, A. (2014). A Rapid and Efficient 2D/3D Nuclear Segmentation Method for Analysis of Early Mouse Embryo and Stem Cell Image Data Stem Cell Reports, 2 (3), 382-397 DOI: 10.1016/j.stemcr.2014.01.010
9.Wen, L., & Tang, F. (2014). Reconstructing Complex Tissues from Single-Cell Analyses Cell, 157 (4), 771-773 DOI: 10.1016/j.cell.2014.04.024
10.Robson, P. (2014). Deciphering Developmental Processes from Single-Cell Transcriptomes Developmental Cell, 29 (3), 260-261 DOI: 10.1016/j.devcel.2014.04.032
We are looking for a Research Assistant to join the Electron Microscope (EM) Facility based in the Sir William Dunn School of Pathology at the University of Oxford.
The successful candidate will assist the EM Facility Manager in two main areas. The first is the day-to-day running of the facility, which will include preparation of chemical solutions, ordering consumables and general lab maintenance. The second will be to undertake work on service projects, which will involve the preparation and imaging of biological specimens for EM, and also to train users in EM specimen preparation techniques (including ultramicrotomy) and on the electron microscopes. There will also be scope to develop the capabilities of the facility in advanced EM techniques, which will involve both independent and collaborative work with researchers.
The Dunn School EM Facility is one of two main hubs for electron microscopy of biological specimens at The University of Oxford. Here, researchers from many different departments across the University image everything from nanoparticles, proteins, viruses and bacteria to cells, tissue and whole organisms, as part of research in diverse range of disciplines, including biomedicine, biophysics, biochemistry and plant biology.
The Facility comprises an FEI Tecnai T12 Transmission Electron Microscope (TEM), a JEOL-6390 Scanning Electron Microscope (SEM) and a dedicated specimen preparation laboratory. This Facility provides its users with a broad range of EM options, from imaging negatively stained particulate samples and thin sections of resin-embedded cells and tissue at the ultrastructural level using TEM, to high resolution topgraphical imaging of cells and whole organisms (eg: C. elegans and Drosophila) with the SEM, through to more advanced techniques including 3D-SEM, EM tomography, correlative light and electron microscopy (CLEM), cryo-ultramicrotomy and protein localisation using immunogold or new genetic tags for EM. Development and optimisation of advanced EM techniques is a key priority for the Facility so that we can continue to provide our expanding user base with access to cutting edge EM methods and technologies.
The post is available as a full time fixed-term contract (Grade 6: £26,527 – £31,644 p.a.) for 2 years in the first instance. If you are interested in this role, and have the skills and experience we are looking for, please apply online. You will be required to upload a CV and supporting statement as part of your online application.
The closing date for applications is 12.00 midday on 13 June 2014. Interviews will be held in the week beginning 16 June 2014.
Decisions, decisions…aren’t those one of our main worries? It is certainly the everyday worry of a stem cell! Understanding stem cell decisions is a central question in the field: how do stem cells manage to keep the right balance between self-renewal (make identical copies of themselves) and differentiation (produce specialized cells)? How do stem cells choose between quiescence and proliferation? Good models to study these decision-making mechanisms are stem cells located in highly renewable tissues, such as the skin, the gut, the blood and the testes, since their specialized cell output is constant and huge.
It is currently known that in these tissues, some stem cells will stay quiescent in order to avoid premature exhaustion. This allows the long-term maintenance of the stem cell population and ensures that organ function is maintained throughout life. However, little is known about how these quiescent stem cells decide to stay quiescent.
In a recent study published in Development, Liao and colleagues showed that the protein Dnmt3l promotes the quiescence of spermatogonial stem cells (stem cells of the testes). They genetically engineered a mouse model in which they switched off the gene producing Dnmt3l (called Dnmt3l KO). They showed that spermatogonial stem cells in Dnmt3l deficient mice were abnormally distributed in the testes and that they proliferated more than in normal mice (wild type).
In this picture you can observe the testes of normal mice (wild type, top of the panel) and of Dnmt3l deficient mice (Dnmt3l KO, bottom of the panel). In wild type mice, the expression of PLZF, a marker for spermatogonial stem cells, is mainly perinuclear (ie: slightly around the nucleus identifiable by Hoescht 33342 in blue), a pattern specific to quiescent stem cells. In Dnmt3l KO mice, the expression of PLZF is mainly punctate (ie: small dots within the nucleus), a pattern specific to active/proliferating stem cells. From this, authors conclude that spermatogonial stem cells in Dnmt3l deficient mice proliferate more than in wild type mice, hence demonstrating a key role of Dnmt3l in regulating the quiescence/proliferation decisions of spermatogonial stem cells.
This study, among many others, is a step closer to a good understanding of how stem cells make decisions between quiescence and proliferation and/or self-renewal and differentiation. These decisions, when good, ensure the maintenance of healthy tissues throughout our lives…Bad decisions however, can lead to disease, and understanding how a stem cell makes the wrong decision is the first step to design a strategy to prevent it!
Picture credit:
Liao, H., Chen, W., Chen, Y., Kao, T., Tseng, Y., Lee, C., Chiu, Y., Lee, P., Lin, Q., Ching, Y., Hata, K., Cheng, W., Tsai, M., Sasaki, H., Ho, H., Wu, S., Huang, Y., Yen, P., & Lin, S. (2014). DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells Development DOI: 10.1242/dev.105130
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