Austin Smith: We study pluripotent stem cells in vitro and their relationship to transient pluripotent cells in mammalian embryos. To execute their potential, naive pluripotent cells must gain lineage competence, a process termed formative transition. We want to understand:
how potency and competence are encoded by a dynamic regulatory network of signals, transcription factors and chromatin
how cells transition between states of competence and how fate decisions are made
how the trajectory and regulatory machinery of pluripotency is adapted in different mammals
The Smith lab
Lab roll call
Tao Huang, post-doc, establishing naïve pluripotent stem cells from non-human primates
Zhili Ren, post-doc, investigating self-renewal and formative transition in human naïve stem cells
Arthur Radley, post-doc, investigating cell identities and trajectories by computational analysis of transcriptome data
Francesca Carlisle, experimental officer, supporting stem cell culture and next generation sequencing, plus lab manager for the group
Zhi (Klein) Zhang, PhD student, studying transition from trophectoderm to amnion competence
Jing Yen Yong, PhD student, studying capacitation of naïve cells for definitive endoderm formation
Favourite technique, and why?
Austin: Stem cell culture, because it is life in our hands – a path to understanding and control.
Apart from your own research, what are you most excited about in developmental and stem cell biology
Austin: The regenerative plasticity uncovered in adult stem cell tissues such as intestine and lung is very interesting. The dedifferentiation seen after injury, or during cancer formation, is a striking contrast to how we generally consider developmental trajectories and more complex than a simple reversal process.
How do you approach managing your group and all the different tasks required in your job?
Austin: My role as Institute Director takes a lot of my time so the people in my group have to be quite independent. Joint lab meetings with the group of Ge Guo who also work on pluripotency are the main forum where group members present and get feedback on their research. I often follow up with 1 to 1 discussion. In general, I like to let people get on with their own experiments and ideas. I get more heavily involved as results emerge and require discussion. I usually take the lead in paper planning and writing.
What is the best thing about where you work?
Austin: The Living Systems Institute combines different research interests. The open space design of our building is ideal for research and social interaction. Labs, facilities, and technical support are all good. We have good community space including an outdoor terrace. The atmosphere is friendly and supportive.
What’s there to do outside of the lab?
Austin: Great outdoors along the river, the Jurassic coast, and Dartmoor, with endless opportunities for recreation, relaxation, and exploration
Browse through other ‘Lab meeting’ posts featuring developmental and stem cell biology labs around the world.
Anchel de Jaime Soguero (COS, University of Heidelberg) ‘Cell signaling control of genome stability during early lineage specification and neurogenesis’
Elena Camacho Aguilar (Rice University) ‘Combinatorial integration of BMP and WNT allows BMP to act as a morphogen in time but not in concentration’
Tyler Huycke (UCSF) ‘Patterning and folding of intestinal villi by active mesenchymal dewetting’
In the third episode of the Human Developmental Biology Initiative‘s new podcast, scientist Magomet ‘Mag’ Aushev, a postdoctoral researcher in Mary Herbert‘s lab at Newcastle University, meets Zara, a songwriter and performer from Manchester. The two discuss the very first cell divisions after an egg is fertilised and why a better understanding of very early development may impact fertility treatment and regenerative medicine of the future.
At the end of the episode, the pair write and record an original piece of music inspired by their conversation, exploring the science of human development in a brand new way.
“It really is like a universe on its own, a single cell.”
– Mag Aushev
Please subscribe and listen to Made the Same Way on Apple podcasts, Spotify, or wherever you get your podcasts. If you enjoy the podcast, please rate and review us on Apple podcasts to help others find us!
About the participants
Prior to joining HDBI, Magomet was applying genome editing for the treatment of genetic diseases and is now using it to generate reporter embryos to study early development. In his spare time Magomet works on machine learning pet projects and plays the guitar.
Zara is a song writer and performer – specialist mic controller (rapper)! She considers herself a philosopher, which comes across in her music, often covering about existential topics – love, happiness , grief, identity, self belief, overcoming trauma.
“By and large, animals have the same genes that you and I have. They’re just using them in a different way that makes it less likely for them to get a disease.”
Dr Linda Goodman, Fauna Bio
In the latest episode of Genetics Unzipped, we’re becoming chromosomal criminals and learning about how researchers are stealing genes from the animal kingdom and using them to improve human health. From 13-lined ground squirrels teaching us how to recover from heart attacks, to bowhead whales showing us how to avoid cancer, there’s a lot geneticists can learn from Mother Nature.
Now in its thirteenth year of serving the developmental and stem cell biology community, the Node continues to be the place for scientists to share research stories, job adverts and event listings. Helen Zenner (previous Community Manager of the Node, now at FocalPlane) and Katherine Brown (Development Executive Editor) recently wrote an Editorial in the journal Development, reviewing some of the Node’s most popular features, as well as introducing some of our newer initiatives.
One highlight for 2023 is the correspondents scheme, a joint project with our sister site FocalPlane (find out more about FocalPlane in this companion Editorial in Journal of Cell Science). For the Node, we have appointed Alexandra Bisia (University of Oxford), Brent Foster (University of Florida) and Dina Myasnikova (University of Tokyo) as the Node correspondents. You can find out more about Alexandra, Brent and Dina in our interviews on the Node, and find their posts collected together at https://thenode.biologists.com/the-node-correspondents/.
The Node Correspondents
The Node only works because of the fantastic engagement from all of you in the developmental and stem cell biology community. Thank you for reading, posting, and contributing to the Node over the years. If you have any ideas or feedback for the Node, don’t hesitate to email us at thenode@biologists.com. Remember, once you are registered with the Node, you are free to contribute, post and comment on the site!
Joseph J Hanly, Ling S Loh, Anyi Mazo-Vargas, Teomie S Rivera-Miranda, Luca Livraghi, Amruta Tendolkar, Christopher R Day, Neringa Liutikaite, Emily A Earls, Olaf BWH Corning, Natalie D’Souza, José J Hermina-Perez, Caroline Mehta, Julia Ainsworth, Matteo Rossi, W. Owen McMillan, Michael W Perry, Arnaud Martin
Shuyao Kong, Mingyuan Zhu, M. Regina Scarpin, David Pan, Longfei Jia, Ryan E. Martinez, Simon Alamos, Batthula Vijaya Lakshmi Vadde, Hernan G. Garcia, Shu-Bing Qian, Jacob O. Brunkard, Adrienne H. K. Roeder
Moises Freitas-Andrade, Cesar H Comin, Peter C Van Dyken, Julie Ouellette, Joanna Raman-Nair, Nicole Blakeley, Quing Yan Liu, Sonia Leclerc, Youlian Pan, Ziying Liu, Micael Carrier, Karan Thakur, Alexandre Savard, Gareth M Rurak, Marie-Eve Tremblay, Natalina Salmaso, Luciano Da F Costa, Gianfilippo Coppola, Baptiste Lacoste
Andrew J Aman, Lauren M Saunders, August A Carr, Sanjay R Srivatsan, Colten Eberhard, Blake Carrington, Dawn E Watkins-Chow, William Pavan, Cole Trapnell, David M. Parichy
Benjamin T. Throesch, Muhammad Khadeesh bin Imtiaz, Rodrigo Muñoz-Castañeda, Masahiro Sakurai, Andrea L. Hartzell, Kiely N. James, Alberto R. Rodriguez, Greg Martin, Giordano Lippi, Sergey Kupriyanov, Zhuhao Wu, Pavel Osten, Juan Carlos Izpisua Belmonte, Jun Wu, Kristin K. Baldwin
Martin Minařík, Melinda S. Modrell, J. Andrew Gillis, Alexander S. Campbell, Isobel Fuller, Rachel Lyne, Gos Micklem, David Gela, Martin Pšenička, Clare V. H. Baker
Edward J. Grow, Ying Liu, Zhiqiang Fan, Iuri Viotti Perisse, Tayler Patrick, Misha Regouski, Sean Shadle, Irina Polejaeva, Kenneth L. White, Bradley R. Cairns
Chengxiang Qiu, Beth K. Martin, Ian C. Welsh, Riza M. Daza, Truc-Mai Le, Xingfan Huang, Eva K. Nichols, Megan L. Taylor, Olivia Fulton, Diana R. O’Day, Anne Roshella Gomes, Saskia Ilcisin, Sanjay Srivatsan, Xinxian Deng, Christine M. Disteche, William Stafford Noble, Nobuhiko Hamazaki, Cecilia B. Moens, David Kimelman, Junyue Cao, Alexander F. Schier, Malte Spielmann, Stephen A. Murray, Cole Trapnell, Jay Shendure
Ivan Imaz-Rosshandler, Christina Rode, Carolina Guibentif, Mai-Linh N. Ton, Parashar Dhapola, Daniel Keitley, Ricard Argelaguet, Fernando J. Calero-Nieto, Jennifer Nichols, John C. Marioni, Marella F.T.R. de Bruijn, Berthold Göttgens
Anoushka Joglekar, Wen Hu, Bei Zhang, Oleksandr Narykov, Mark Diekhans, Jennifer Balacco, Lishomwa C Ndhlovu, Teresa A Milner, Olivier Fedrigo, Erich D Jarvis, Gloria Sheynkman, Dmitry Korkin, M. Elizabeth Ross, Hagen U. Tilgner
Hisato Yagi, Cheng Cui, Manush Saydmohammed, George Gabriel, Candice Baker, William Devine, Yijen Wu, Jiuann-huey Lin, Marcus Malek, Abha Bais, Stephen Murray, Bruce Aronow, Michael Tsang, Dennis Kostka, Cecilia W. Lo
Left-right differential gene expression from Yagi et al.
David Bolumar, Javier Moncayo-Arlandi, Javier Gonzalez-Fernandez, Ana Ochando, Inmaculada Moreno, Carlos Marin, Antonio Diez, Paula Fabra, Miguel Ángel Checa, Juan José Espinos, David K. Gardner, Carlos Simon, Felipe Vilella
Nana Matoba, Brandon D Le, Jordan M Valone, Justin M Wolter, Jessica Mory, Dan Liang, Nil Aygün, K Alaine Broadaway, Marielle L Bond, Karen L Mohlke, Mark J Zylka, Michael I Love, Jason L Stein
Heather L. Dingwall, Reiko R. Tomizawa, Adam Aharoni, Peng Hu, Qi Qiu, Blerina Kokalari, Serenity M. Martinez, Joan C. Donahue, Daniel Aldea, Meryl Mendoza, Ian A. Glass, Birth Defects Research Laboratory (BDRL), Hao Wu, Yana G. Kamberov
Daniela Doda, Sara Alonso Jimenez, Hubert Rehrauer, Jose F. Carreño, Victoria Valsamides, Stefano Di Santo, Hans Ruedi Widmer, Albert Edge, Heiko Locher, Wouter van der Valk, Jingyuan Zhang, Karl R. Koehler, Marta Roccio
Florentine Dylong, Jan Riedel, Gaurang M. Amonkar, Nicole Peukert, Paula Lieckfeldt, Katinka Sturm, Benedikt Höxter, Wai Hei Tse, Yuichiro Miyake, Steffi Mayer, Richard Keijzer, Martin Lacher, Xingbin Ai, Jan-Hendrik Gosemann, Richard Wagner
Clara Morral, Arshad Ayyaz, Hsuan-Cheng Kuo, Mardi Fink, Ioannis Verginadis, Andrea R. Daniel, Danielle N. Burner, Lucy M. Driver, Sloane Satow, Stephanie Hasapis, Reem Ghinnagow, Lixia Luo, Yan Ma, Laura D. Attardi, Costas Koumenis, Andy J Minn, Jeffrey L. Wrana, Chang-Lung Lee, David G. Kirsch
Shruthi Subramanian, Julie A.I. Thoms, Yizhou Huang, Paola Cornejo, Forrest C. Koch, Sebastien Jacquelin, Sylvie Shen, Emma Song, Swapna Joshi, Chris Brownlee, Petter S. Woll, Diego Chacon Fajardo, Dominik Beck, David J. Curtis, Kenneth Yehson, Vicki Antonenas, Tracey O’ Brien, Annette Trickett, Jason A. Powell, Ian D. Lewis, Stuart M. Pitson, Maher K. Gandhi, Steven W. Lane, Fatemeh Vafaee, Emily S. Wong, Berthold Göttgens, Hamid Alinejad Rokny, Jason W.H Wong, John E. Pimanda
Ambre Guillory, Mauricio Lopez-Obando, Khalissa Bouchenine, Philippe Le Bris, Alain Lécureuil, Jean-Paul Pillot, Vincent Steinmetz, François-Didier Boyer, Catherine Rameau, Alexandre de Saint Germain, Sandrine Bonhomme
Brennan Hyden, Dana L. Carper, Paul E. Abraham, Guoliang Yuan, Tao Yao, Leo Baumgart, Yu Zhang, Cindy Chen, Ronan O’Malley, Jin-Gui Chen, Xiaohan Yang, Robert L. Hettich, Gerald A. Tuskan, Lawrence B. Smart
Juliane Tschuck, Vidya Padmanabhan Nair, Ana Galhoz, Gabriele Ciceri, Ina Rothenaigner, Jason Tchieu, Hin-Man Tai, Brent R. Stockwell, Lorenz Studer, Michael P. Menden, Michelle Vincendeau, Kamyar Hadian
Robert Hardt, Alireza Dehghani, Carmen Schoor, Markus Gödderz, Nur Cengiz Winter, Shiva Ahmadi, Ramesh Sharma, Karin Schork, Martin Eisenacher, Volkmar Gieselmann, Dominic Winter
Ran Wang, Xianfa Yang, Jiehui Chen, Lin Zhang, Jonathan A. Griffiths, Guizhong Cui, Yingying Chen, Yun Qian, Guangdun Peng, Jinsong Li, Liantang Wang, John C. Marioni, Patrick P.L. Tam, Naihe Jing
Soumyaroop Bhattacharya, Caroline Cherry, Gail Deutsch, Birth Defects Research Laboratory (BDRL), Ian A. Glass, Thomas J. Mariani, Denise Al Alam, Soula Danopoulos
Tomas Wald, Adya Verma, Victoria Cooley, Pauline Marangoni, Oscar Cazares, Amnon Sharir, Evelyn J. Sandoval, David Sung, Hadis Najibi, Tingsheng Yu Drennon, Jeffrey O. Bush, Derk Joester, Ophir D. Klein
Luca Deininger, Sabine Jung-Klawitter, Petra Richter, Manuel Fischer, Kianush Karimian-Jazi, Michael O. Breckwoldt, Martin Bendszus, Sabine Heiland, Jens Kleesiek, Ralf Mikut, Daniel Hübschmann, Daniel Schwarz
Cheng-Yu Li, Helena Boldt, Emily Parent, Jax Ficklin, Althea James, Troy J. Anlage, Lena M. Boyer, Brianna R. Pierce, Kellee Siegfried, Matthew P. Harris, Eric S. Haag
Dr Liam Barry-Carroll, Dr David A Menassa, Professor Diego Gomez-Nicola and colleagues have recently published a paper in Cell Reports elucidating the mechanisms by which microglial cells expand as a population in the mouse brain using fate-mapping approaches. We asked Dr Barry-Carroll to give us a behind the scenes look into how the story came together.
How did you get started on the project?
I started working on the project when I joined the Gomez-Nicola lab in 2017 to start my PhD. I had been interested in studying microglia and so I applied for the position on a website called findaphd.com and was lucky to be accepted. For me it was interesting to study the cells in a healthy context which can be so often overlooked in the field.
What was already known about microglial colonisation and expansion in rodents?
Studies coming out in the 1990s were able to demonstrate that progenitors of microglia were highly proliferative and subsequent studies had shown that a relatively small number of microglia progenitors go on to colonise the entire brain in just a short timespan during early postnatal life. However, it was unknown whether this was through clonal expansion or whether it was a more stochastic process of random proliferation of all the cells, as is the case of microglia in the healthy adult brain. Interestingly we can gain some insight from disease models whereby fate mapping studies have demonstrated that microglia will clonally expand in response to injury or disease. Our goal here was to see which of these potential mechanisms is responsible for the developmental colonisation of the brain by microglia.
Can you summarise your findings?
Here we were able to build on the findings of previous studies and showed that microglia expand quite rapidly, particularly during early development and that this expansion is correlated with the growth of the brain. As development continues, we could see changes in the spatiotemporal distribution of microglia from more dense clusters until late postnatal development (P21) when they formed a tiled or mosaic distribution allowing them to really cover the entire cortex and parenchyma. Using two methods of fate mapping, we demonstrated that microglial progenitors clonally expand during embryonic and postnatal development. Our multicolour lentiviral labelling approach allowed us to carry out clone-by-clone analysis and we observed that the mosaic of microglia is made up of inter-locking clones ranging in size from a couple of cells to quite large clones, indicating a disparity in the proliferative rate of different microglial progenitors during development. Subsequent mathematical modelling confirmed our finding that the proliferative potential is heterogenous among microglial progenitors. Another interesting finding was that microglia from larger clones tended to be spatially associated which may result in clonal dominance in certain brain regions.
Figure 1 Summary of experimental methods used to show how microglia expand in the mouse brain.
When doing your research, did you have a eureka moment that has stuck with you?
For me, the moment came when I applied the spatial analysis to the different experimental setups, that is when we could clearly see the same spatial trends present in our different set-ups.
What about the flipside? Any moments of despair or frustration?
There were some moments of despair, particularly in the beginning when we were testing different multicolour reporters to much less avail. Eventually it came down to a promoter that was not efficiently expressed in microglia. We managed to overcome this hurdle by setting up the sparse-labelling protocol as suggested by Dr Salah Elias (University of Southampton) who is a developmental scientist.
Where will this story take you next?
For now, I have finished this project and started a postdoc in the Nutrineuro laboratory in Bordeaux, France. However, I cannot say that I wouldn’t like to revisit this topic in the future, and I hope that our study will inspire some more research into this area, particularly in understanding the molecular mechanisms involved in the regulation of microglial proliferation and the potential sources of this proliferative heterogeneity.
What is next for you after this paper?
As I said, I have recently started my journey as a postdoc with Dr Jean-Christophe Delpech and Dr Sophie Layé and I am applying my knowledge of microglia in the field of extracellular vesicles. I am really looking forward to seeing how I can combine these different research topics and all that I have learned and ultimately build my future research career. Exciting times ahead!
We are in the Faculty of Biology, Medicine and Health at the University of Manchester.
Research summary
Hilary Ashe: We aim to understand how cell signalling and gene expression dynamics control developmental patterning, using the Drosophila embryo and ovarian germline stem cells as models.
The Ashe lab
Lab roll call
Catherine Sutcliffe, Research Technician, provides lab support and contributes to research projects including germline stem cell regulation in the Drosophila ovary.
Lauren Forbes Beadle, Postdoctoral research associate, studying how dynamic transcription underpins developmental processes in the early Drosophila embryo.
Nabarun Nandy, Postdoctoral research associate, studying the genetic and cellular mechanisms responsible for Drosophila ovarian germline stem cell maintenance.
Alastair Pizzey, Postdoctoral research associate, studying translation dynamics in the early Drosophila embryo, using single molecule imaging.
Jennifer Love, PhD student, using quantitative approaches to investigate the role of mRNA degradation in early Drosophila development.
Gareth Moore, PhD student, studying the extracellular regulation of Bone Morphogenetic Protein Signalling in development and disease.
Favourite technique, and why?
Hilary: In situ hybridisation as I think it is amazing to be able to visualise tissue specific expression patterns throughout development. I love how it has stood the test of time, evolving to allow single mRNA imaging and spatial transcriptomics.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Hilary: The progress in, and potential for, dissecting patterning and morphogenesis in synthetic embryos, including human embryoids, is very exciting. I also like how cross species comparisons of developmental processes in organoids from different species are being used to study developmental timing.
How do you approach managing your group and all the different tasks required in your job?
Hilary: In addition to our weekly lab meeting, I meet individually with everyone in the lab once a week to discuss their projects. Juggling all the different tasks is always a challenge but I try to protect blocks of time for research-related tasks and keep on top of everything with a to do list of priorities.
What is the best thing about where you work?
Hilary: Great core facilities and some fantastic colleagues doing really interesting research.
Cath: The facilities and resources which are available at the University including Bioimaging and the Fly Facility
Lauren: Collaborative and friendly research environment.
Nabarun: Warm, friendly and extremely supportive environment alongside the easy access to cutting edge tools for cellular and molecular studies.
Ali: The collaborative environment and the facilities, particularly the selection of microscopes.
Jenny: Lots of opportunities to get involved in widening participation and social causes at UoM.
Gareth: The breadth of research going on at Manchester means there’s always someone to talk to, to solve a problem or try a new idea.
What’s there to do outside of the lab?
Hilary: Manchester has everything except a beach!
Cath: Close to the peak district, restaurants, football, museums
Lauren: The variety of cuisines/restaurants and live music.
Nabarun: Cosmopolitan culture of the city offers a huge range of places to explore and eat.
Ali: Excellent places for music, coffee and beer.
Jenny: Manchester has something for everyone from creatives, with the lively music and arts scene, to the more outdoorsy folk getting lost in the peak district.
Gareth: Finding the best coffee in Manchester (an endless joy) and access to great hiking (joyless if unending).
Browse through other ‘Lab meeting’ posts featuring developmental and stem cell biology labs around the world.
I think there was concerns about it being a big project and being big science and team science that, you know, worked well for Apollo missions, that worked well in physics and chemistry, but you know, biomedical researchers up until that point, never did big science projects. They were just unheard of.
Dr Eric Green
Earlier this week was DNA Day, which this year marks both the 20th anniversary of the Human Genome Project’s completion and the 70th anniversary of the discovery of the DNA double helix. To celebrate, we are rereleasing an episode from Series 3, when Kat interviewed the director of the US National Human Genome Research Institute, Dr Eric Green about his work on the Human Genome Project from its very inception.
If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
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