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  Newsletter Issue 7, 28 October 2013

Gold Sponsors

 

STEM CELL SOCIETY SYMPOSIUM 2013

"Early Human Development & Fetal-Maternal Medicine"

18 -19 November

Matrix Building Level 2 & 2M
30 Biopolis Street, Singapore 138671

Silver Sponsors

 

Bronze Sponsors

Dear Members, Delegates, Friends, and Colleagues,

The Symposium 2013 Newsletter, Issue 7 features abstracts, bios and questionnaires of Pathik Wadhwa from UC Irvine, Florent Ginhoux, from the Singapore Immunology Network, and Jia Hui Ng from the Genome Institute of Singapore.

We also present the abstract selected speaker Ernesto Lujan from the Stanford University School of Medicine.

COUNT DOWN: there are 20 days left to the symposium only!!! And only 6 days to submit your online registration.

Updates:

Programme: The tentative programme can be viewed here.

Symposium hotel: The Park Avenue Rochester Hotel which is just across the road and in walking distance to the symposium venue is the ideal hotel for your stay during in Singapore. It l is conveniently located close to public transport facilities such as the bus and the MRT networks. Considering staying in this hotel? Click here for more information.

Delegate Networking Event: A networking event open to all delegates of the symposium will take place on the first evening (18th November). Venue will be the Epicentre at Biopolis. Drinks and food should help stimulating interactions and communications among delegates.

DEADLINES:

IMPORTANT: Online Registration closes in 6 days!!

So hurry and register before the 4 November 2013!

To register, click HERE.

To learn more about the symposium, follow this LINK.

Contact us HERE.

Register today to enjoy excellent science and the networking opportunity with your colleagues and collaborators,

The Organizing Committee Stem Cell Society Singapore Symposium 2013

 

 

Featured Speakers  

Pathik WADHWA

UC Irvine, USA

 
Abstract  
Fetal Programming of Human Health and Disease Risk: Role of Prenatal Stress and Stress Biology

 

The UC Irvine Development, Health and Disease Research Program is a trans-disciplinary, translational effort to elucidate the nature and consequences of the interplay between biological, behavioral, social and environmental conditions during early human development (intrauterine and early postnatal life) on health and disease-risk related outcomes over the lifespan. Outcomes of interest include fetal growth and maturation, birth phenotypes, and newborn, infant and child physical and mental health. Mechanisms of interest include maternal-placental-fetal endocrine, immune, vascular and genetic/epigenetic processes, with a particular focus on telomere and mitochondrial biology.

Our initial studies have found that after accounting for the effects of established sociodemographic and obstetric risk factors, maternal stress exposure during pregnancy is significantly and independently associated with increased risk of adverse pregnancy and birth outcomes related to the length of gestation and fetal growth, and that these effects are mediated, in part, by stress-related alterations in maternal-placental-fetal endocrine and immune processes.

Maternal stress also increased the risk of developing reproductive tract infection during pregnancy and potentiating its pathophysiological consequences.  In subsequent studies we examined the effects of maternal prenatal stress exposure on longer-term health outcomes. Findings suggest that individuals (young adults) exposed during intrauterine life to maternal stress exhibited significant alterations in metabolic function (higher percent body fat, primary insulin resistance, and a lipid profile consistent with the metabolic syndrome), immune function (a TH2 shift in the TH1/TH2 balance, consistent with increased risk of asthma and atopic disorders), endocrine function (increased adrenocorticotropic hormone (ACTH) and reduced cortisol concentrations during pharmacological and psychological stimulation paradigms, consistent with the high-risk endocrine profile exhibited by individuals exposed to early life abuse), cognitive function (impaired prefrontal cortex (PFC)-related working memory performance after hydrocortisone administration), and accelerated rate of cellular aging (reduced leukocyte telomere length).

Biography PubMed

 

Pathik D. Wadhwa is a tenured Professor at the University of California, Irvine, School of Medicine, with a primary appointment in Psychiatry & Human Behavior and joint appointments in Obstetrics & Gynecology, Pediatrics, and Epidemiology. He also is the founding Director of the UC Irvine Development, Health and Disease Research Program. Dr. Wadhwa received his medical degree from the University of Poona, India, in 1985, and his doctorate in behavioral medicine from the University of California, Irvine, in 1993. His research examines the interface between biological, social and behavioral processes in human pregnancy, with an emphasis on outcomes related to fetal development, birth, and subsequent newborn, infant and child development and health. In particular, this work focuses on the role of maternal-placental- fetal neuroendocrine, immune and genetic/epigenetic processes as putative mechanisms that mediate the effects of the maternal environment, and particularly of prenatal stress, on early human development.

Dr. Wadhwa is the primary author or co-author of numerous publications in this area. His research has continuously been supported by several grants primarily from the National Institutes of Health. Dr. Wadhwa served from 2005-2012 as the Co-Principal Investigator of the Orange County, California (OCCA) Vanguard Center of the U.S. National Children’s Study (NCS), the largest and most comprehensive study to date of genetic and environmental influences on child development and health. Dr. Wadhwa is the recipient of several honors and awards, including recognition for his career contributions from the Academy of Behavioral Medicine, the Perinatal Research Society, the National Institutes of Health, the U.S. Library of Congress, and the World Health Organization.

Interview  

What is your most memorable career achievement?

Watching my postdoctoral trainees transition to becoming independent researchers and obtaining their own NIH RO1 awards.

What attracted you to a career in Science/Research?

The joy of being able to ask and pursue questions of interest and the sense of exploration that’s part of the journey.

Who are your scientific heroes/role models and why?

All those who pursue questions and learning for its own sake and not necessarily as a means to an end.

What would you be if not a scientist/clinician?

Probably an executive in a business corporation or an attorney.

What's the best advice you ever had?

Nothing specific comes to mind. I generally do not rely on anyone’s advice but try to develop my own opinions.

What’s your motto in life?

Do the best you can do in whatever you’re trying to do and never give up.

What would you tell a student asking you for advice whether to pick up a career in clinical research?

To ask the student to try to the best of her/his ability to find out whether the process of doing research is fulfilling for its own sake and not as a means to a specific end.

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Jia Hui NG

Genome Institute of Singapore

 

 
Abstract  
In Vivo Epigenomic Profiling of Germ Cells Reveals Germ Cell Molecular Signatures  

Germ cells are unipotent cells that give rise to mature gametes. In the developing embryo, germ cells undergo genome-wide reprogramming that erases and re-establishes DNA methylation and certain histone marks, a process thought to be important for post-fertilization development. Remarkably, germ cells also retain the plasticity to acquire pluripotency in vitro if provided with the appropriate cell culture conditions.

While it is known that early fetal germ cells express some pluripotency genes such as Pou5f1, the epigenome of germ cells is not well understood due to limited cell numbers and technical challenges. Here, we performed transcriptional profiling and ChIP-Seq on in vivo fetal germ cells to investigate the molecular signatures of germ cells and compare this with other cell types.

Biography PubMed  

Jia-Hui Ng graduated with B.Sc (Hons.) in Life Sciences from the National University of Singapore, where she was awarded the Lijen Industrial Development Medal in 2007. Supported by the A*STAR graduate scholarship, she worked on iPSC reprogramming and germ cell profiling under the supervision of Dr Huck-Hui Ng at the

Genome Institute of Singapore (GIS) and obtained her PhD in 2012. She continues working as a post-doctoral research fellow in GIS, and her research is focused on small-scale ChIP-Seq and stem cells

Interview  

What was the first phenomenon you can recall that fascinated you to do science?

During my first laboratory experience, I was working with plant cells which upon wounding can dedifferentiate and regenerate into whole plants again. This fascinating developmental plasticity, also known as totipotency, is lost in mammals as the zygote develops and only regained through the process of fertilization.

What attracted you to a career in Science?

Intellectual freedom and flexibility. Every day is different and we are constantly learning from one another.

What are the main issues confronting stem cell researcher?

One beauty of (some types of) stem cells is that they could be maintained in vitro for prolonged periods. However, it is difficult to ensure that they remain normal in the dish.

Which is the single most factor driving or inhibiting the broad clinical application of stem cells?

Safety issues that we have yet to fully comprehend.

What would you be if not a scientist/clinician?

I love to be around animals. Probably a veterinarian.

What's the best advice you ever had?

We can always gain something from failed attempts, and use that to overcome the bend in the road.

What will be the next major breakthrough in stem cell research?

The ability to stimulat and control stem cell in-vivo.

 

Florent GINHOUX

Singapore Immunology Network

 

 

 

 
Abstract  
Differentiation and Characterization of Microglial Precursors from Pluripotent Stem Cells  
Microglia are the resident macrophage population of the central nervous system (CNS). Adequate microglial function is crucial for a healthy CNS; microglia are not only the first immune sentinels of infection and inflammation, but are also involved in the maintenance of brain homeostasis. Consequently, microglial dysfunction is implicated in the pathophysiology of many neurological disorders. Functionally relevant microglial precursors generated in vitro would be useful for investigating microglial activation and response to drug treatment, and contribute towards the development of cell-based therapies. Importantly, microglia are derived from primitive macrophage progenitors arising in the extra-embryonic yolk sac (YS). As ES/iPS cells in vitro differentiation closely recapitulates the temporal stages of YS hematopoiesis, we seek to generate ES/iPS cells-derived primitive macrophage progenitors as microglial precursors. ES/iPS cells were differentiated in vitro using a serum-free protocol. Pure populations of primitive-like macrophages were obtained after 10-12 days of culture. Both ES and iPS-derived populations were phenotypically similar to the primitive macrophages derived from embryonic YS and brain rudiment in terms of surface marker expression as well as expression of pro-inflammatory genes in response to microglial activating factors. Global gene expression profiles from microarray analysis of pluripotent cell-derived populations were also closely aligned with those of primary cells. Further in vivo studies are currently under way to evaluate the long-term integration and survival of pluripotent cell-derived precursors in the neonatal brain. Our differentiation strategy is a reliable and efficient method of obtaining microglial precursors suitable for functional assays, high-throughput screening, as well as potential cell transplantation therapies.
Biography PubMed  
Florent Ginhoux graduated in Biochemistry from the University Pierre et Marie CURIE, Paris VI and obtained a Masters degree in Advanced Studies in Immunology from the Pasteur Institute, Paris. He then started his PhD in the Immunology Team of GENETHON, Evry and obtained his PhD in 2004 from the University Pierre et Marie CURIE, Paris VI. As a postdoctoral fellow, Florent Ginhoux joined the Laboratory of Miriam Merad in the Mount Sinai School of Medicine (MSSM), New York where he studied the ontogeny and the homeostasis of dendritic cell populations, with a strong focus on Langerhans cells. In 2008, he became an Assistant Professor in the Department of Gene and Cell Medicine, MSSM and member of the Immunology Institute of MSSM. He joined the Singapore Immunology Network (SIgN), A*STAR in May 2009 as a Principal Investigator. His laboratory is now focusing on the ontogeny and differentiation of macrophages and dendritic cells in both humans and mice. His group recently discovered that microglia, the resident macrophages of the central nervous system derive from early embryonic yolk sac (YS) primitive macrophages (Ginhoux, Science 2010). As YS hematopoiesis can be recapitulated in vitro with embryonic stem cells (ESCs) and “induced pluripotent stem cell” (iPSC), he is now closely collaborating with Dr Tara Huber of the Genome Institute of Singapore (GIS), to apply this knowledge to develop novel differentiation protocols to generate microglia from iPSC. This approach could open new avenues for the treatment of brain inflammatory diseases as microglia are intimately involved in the pathology of such diseases.
Interview  

What was the first phenomenon you can recall that fascinated you to do science?

The DNA double helix.

What attracted you to a career in Science?

Freedom and the fact that everyday is different..

What is your most memorable career achievement?

When I analyzed the first fate mapping experiment aiming at probing the origin of adult microglia and realized that our hypothesis of their yolk sac origin was true!.

Which scientist/clinician has made the biggest impact in your field and why?

Professor Ralph M. Steinman for the discovery of dendritic cells.

What paper(s) had the most influence on you and why?

The paper from my postdoc mentor, Professor Miriam Merad that showed that epidermal Langerhans cells, although being

hemapoietic cells, self-renew locally throughout life with anycontribution from adult bone marrow hemapoietic stem cells (Merad, Nature Immunology 2002). This paper is the reason why I choose to join her lab in New York in 2004 and also initiated my reserch on the origin of macrophages.

What influenced you to pursue stem cell research?

The possibility to make everything in a plastic dish..

What would you be if not a scientist/clinician?

I will probably have a book store..

What's the best advice you ever had?

To never give up..

What's the best advice you ever had?

To never give up.

Abstract Selected Speaker  

Ernesto LUJAN

Stanford University School of Medicine

 
Abstract  
Mapping iSPC reprogramming by single cell mass cytometry  
Reprogramming somatic cells to a pluripotent state by forced expression of transcription factors is a highly dynamic process. While extremely useful, this process is currently inefficient and the generation of heterogeneous populations over time impedes molecular analysis. In an effort to tease apart this heterogeneity we have utilized single cell mass cytometry. Like conventional fluorescent flow cytometry, this technique allows for the profiling of whole populations at the single cell level in a high-throughput manner; unlike conventional flow, we are able to detect protein levels for up to 30 intra and extra-cellular epitopes per cell with little spectral overlap due to distinct conjugated metal isotopes. With mass cytometry we have analyzed reprogramming factor stoichiometry, post-translational modifications of cell cycle and signaling proteins, pluripotency marker activation, and surface marker profiles for three different reprogramming lines, characterized partially reprogrammed lines, mouse ESCs and mouse iPSCs. From these analyses we find that reprogramming across different systems follows similar stepwise stages which can be clustered into 1) the repression of fibroblast specific markers 2) the emergence of an Oct4high Klf4high population 3) which gives rise to a population that resembles partially reprogrammed cells in cell cycle parameters and surface marker expression. These cells progress into fully reprogrammed Nanoghigh Sox2high CD54high and nonproductive Lin28high Nanoglow CD24high populations. Further, we have used these profiles in combination with novel surface markers to find productive routes to iPSC reprogramming. Our findings show that single cell analysis by mass cytometry can parse productive and nonproductive routes to reprogramming furthering our understanding of pluripotency induction.
Biography PubMed  
Ernesto earned his B.Sc. degree from the University of California, Irvine (UCI) and is a researcher in the Genetics department and Institute for Stem Cell Biology and Regenerative Medicine at Stanford University. While in Marius Wernig’s lab, he found that the combination of Sox2, Brn2 and FoxG1 could directly convert mouse fibroblasts into neural stem cells which could engraft and integrate into the mouse brain. His current work involves understanding how somatic cells acquire pluripotency by using single cell mass cytometry to parse productive and nonproductive routes. He was a California Insititute of Regenerative Medicine (CIRM) predoctoral scholar and is currently a National Science Foundation (NSF) fellow.
Interview  

What is your most memorable career achievement?

Directly converting mouse skin cells into neural stem cells.

Which scientist/clinician has made the biggest impact in your field and why?

Takahashi and Yamanaka are definitely the obvious answers as they were able to show that transcription factors alone could induce the dramatic conversion of somatic cells into pluripotent cells. Of course, the use of transcription factors in reprogramming was built on the work of Lassar and Graf who respectively showed that MyoD or C/EBPs could convert similarly related cell types. Recently, Marius Wernig has really pushed the field forward by showing that distantly related somatic cell types can be efficiently converted with the right combination of transcription factors. This has been impactful because it suggests that a pluripotent state may not be necessary for many applications. Now much of the field is using this paradigm to find the correct combination of transcription factors to convert cells into many clinically and experimentally useful cell types which may be hard to obtain from tissues or differentiation alone.

What paper(s) had the most influence on you and why?

The early Nüsslein-Volhard papers were influential when I was entering science as they demonstrated the power of genetic screens in higher organisms for deconvoluting complex processes.

As for getting into the reprogramming field, Yamanaka’s human and mouse iPSC papers and Marius Wernig’s induced neuronal paper definitely had large influences on my choice to study transdifferentiation.

What influenced you to pursue stem cell research?

Many interesting questions in an applicable field.

What are the main issues confronting stem cell researchers?

Specificity, studies showing in vivo engraftment and functional integration.

What would you be if not a scientist/clinician?

Writer or lawyer.

What is the most promising direction in stem cell research?

Patient specific therapies.