Best Poster Awards – EMBO|EMBL Symposium: Organoids 2020

The recent virtual EMBO|EMBL Symposium on Organ Development and Disease in 3D Culture saw the highest number of registrations we have had since we launched the format. A total of 880 researchers from around the world got together online to discuss recent developments in the formation and maintenance of organoids and their use in disease studies and regenerative medicine.

Out of the 200 digital posters that were presented at the three poster sessions, four were distinguished with a poster prize by a committee appointed by the scientific organisers. Here are the winners:

Organoids model transcriptional hallmarks of oncogenic KRAS activation in lung epithelial progenitor cells

PHOTO: Antonella Dost

Authors: Aaron Moye (1), Antonella Dost (1), Marall Vedaie (2), Linh Tran (5), Eileen Fung (5), Dar Heinze (2), Carlos Villacorta-Martin (2), Jessie Huang (2), Ryan Hekman (2), Julian Kwan Kwan (2), Benjamin Blum (2), Sharon Louie (1), Sam Rowbotham (1), Julio Sainz de Aja (1), Mary Piper (4), Preetida Bhetariya (4), Roderick Bronson (3), Andrew Emili (2), Gustavo Mostoslavsky (2), Gregory Fishbein (5), William Wallace (5), Kostyantyn Krysan (5), Steven Dubinett (5), Jane Yanagawa (5), Darrell Kotton (2), Carla Kim (1)

Presenter: Antonella Dost (1)

Mutant KRAS is the most common oncogenic driver of epithelial cancers. Nevertheless, the molecular changes induced by KRAS activation in primary epithelial cells beyond activation of proliferation remain elusive. Here, we determined transcriptional changes at single-cell resolution after KRAS activation in distal lung epithelial cell populations. We developed a new in vitro organoid system to define the early oncogenic KRAS transcriptional program and model early-stage lung adenocarcinoma (LUAD) using primary murine lung cells. Alveolar epithelial progenitor (AT2) cells expressing oncogenic KRAS lost their mature identity and acquired a transcriptional program similar to lung development and progenitor cells. Similar changes were observed in an early-stage LUAD mouse model, in human induced pluripotent stem cell derived AT2 cells, and in stage I lung cancer patient samples, validating our organoid model. While these events have been observed in advanced lung cancers in mice and humans, we show that KRAS induced dedifferentiation occurs in early-stage lung cancer. This work provides a new organoid tool to rapidly recapitulate lung cancer progression in vitro and a window into the transcriptional changes that immediately follow oncogenic KRAS expression in epithelial cells, revealing candidate targets for early intervention of KRAS-driven lung cancer.

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(1) Boston Children’s Hospital, United States of America
(2) Boston University, United States of America
(3) Harvard Medical School, United States of America
(4) Harvard T. C. Chan School of Public Health, United States of America
(5) University of California Los Angeles, United States of America

Using human pluripotent stem cell-derived organoids to investigate regional-specific features of the small intestine

PHOTO: Guillermo Sanchez

Authors: J Guillermo Sanchez, Heather McCauley, Jacob Enriquez, James Wells, Cincinnati Children’s Hospital, United States of America

Presenter: J Guillermo Sanchez

The gastrointestinal tract is the largest endocrine organ in the body. Specialised nutrient sensing cells, called enteroendocrine cells, are embedded in the intestinal epithelium and secrete over 20 hormones that regulate processes such as satiety, gut motility and gastric emptying. Directed differentiation of human pluripotent stem cells into human intestinal organoids has been used to study and mimic intestinal development; however, most of these models generate intestinal tissue which resembles duodenum and proximal jejunum (Spence, et al 2011). The intestine displays distinct regional functions along the proximal-distal axis, with the ileum being important for unique enteroendocrine hormone secretion, bile acid resorption and interactions with the microbiome. It is known that major signaling pathways such as Wnt, FGF and BMP can affect the regional identity of the developing GI tract. Consistent with previous studies (Munera, Tsai) we found that manipulation of the exposure time of intestinal spheroids to these signaling pathways generated distal intestinal tissue by expression of epithelial markers, nutrient transporters, and hormone expression. These distally-patterned human intestinal organoids retain their regional identity after transplantation in vivo, and can be used to generate epithelial-only enteroid cultures. It remains unknown how diverse cellular types and functions are established along the proximal-distal axis of the small intestine. This model enables us to compare the early transcriptional changes involved in conferring regional-specific features, including enteroendocrine cell allocation, to the GI tract.

Poster currently not available

Recapitulating the somitogenesis in vitro to identify novel causative genes for congenital bone diseases

PHOTO: Marina Matsumiya

Authors: Marina Matsumiya (1), Mitsuhiro Matsuda (1), Nao Otomo (2), Yoshiro Yonezawa (2), Shiro Ikegawa (2), Miki Ebisuya (1)

Presenter: Marina Matsumiya

Somites are periodically formed though the segmentation of anterior parts of presomitic mesoderm (PSM) in embryos. This periodicity is controlled by the segmentation clock gene Hes7, which exhibits a wave-like oscillatory expression in the PSM. The periodical somite formation is a crucial event for body segment formation and abnormal somitogenesis leads to congenital bone diseases.

Spondylocostal dysostosis (SCD) is a bone malformation disease which is characterised by morphological abnormalities of vertebrae and ribs. Mutations in several somitogenesis-related genes, including HES7, are already known as the cause of SCD. As for 75% of SCD patients, however, the causative gene and at what stage of bone development the abnormality occurs are still unclear.

Thus, the aim of this study is to establish a method to recapitulate the somitogenesis in vitro and to identify novel a causative gene of SCD.

To recapitulate the somitogenesis in vitro, we previously reported a simple and efficient method to generate mouse embryonic stem (ES) cell-derived PSM-like tissues (Matsumiya et al., Development, 2018). In these tissues, Hes7 oscillation was synchronized among neighboring cells, the anterior-posterior axis was self-organised, and somite-like structures were observed. We are currently developing a similar method to recapitulate the human somitogenesis by using human induced pluripotent stem (iPS) cells instead mouse ES cells. Furthermore, by using human iPS cell lines that lack the candidate gene of SCD for the in vitro somitogenesis, we are trying to identify a novel causative gene of SCD.

Poster currently not available

(1) EMBL Barcelona, Spain
(2) RIKEN Center for Integrative Medical Sciences, Japan

Heme oxygenase 1 upregulation is induced by stress via alpha-synuclein aggregation in transgenic mice and in Parkinson’s disease derived brain organoids

PHOTO: Silke Frahm-Barske

Authors: Silke Frahm-Barske (2), Sebastian Diecke (2), Franz Theuring (1)

Presenter: Silke Frahm-Barske

Excessive accumulation of alpha-synuclein (a-syn) predisposes to the development of Parkinson’s disease (PD), a disorder characterised by neurodegeneration in the substantia nigra and concomitant motor impairments. It was previously shown that stress-induced release of glucocorticoids accelerates the progression of PD and that the glucocorticoid receptor (GR) is downregulated in several neurodegenerative as well as in stress-related diseases. The impact of altered a-syn protein levels on GR dysfunction and stress-related protein expression is largely unexplored, but may have severe implications for PD manifestation and disease progression. Therefore, we examined the effect of chronic stress in two models overexpressing human a-syn: a transgenic mouse model (h-a-synL62) and brain organoids derived from iPSCs of a PD patient. Wildtype mice that underwent daily restraint for 6 weeks presented typical chronic stress induced features, such as GR-deficiency and increased a-syn protein levels in prefrontal cortex and hippocampus. Importantly, these molecular alterations were reproduced in forebrain organoids generated from healthy donors after treatment with the synthetic glucocorticoid Dexamethasone for 2 weeks. In contrast, glucocorticoid exposure had no effect on GR expression and normalised the level of a-syn in h-a-synL62 mice and PD brain organoids. Accordingly, heme oxygenase 1 (HO-1), an antioxidant protein that can be induced by soluble oligomers and protofibrils and that triggers proteosomal degradation of a-syn, was upregulated. Together, our work provides a new link between a-syn overexpression, GR-deficiency and oxidative stress and their contribution to the development and progression of PD. Further, we established and validated a human 3D tissue culture model that can be used to study stress related diseases, offering replacement of research animals exposed to disturbing procedures.

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(1) Charité – University Medicine Berlin, Germany
(2) Max-Delbrück-Center, Germany

Working on your own conference poster? Then check out these 8 tips for preparing a digital poster that stands out from the crowd.

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Organoids: Modelling Organ Development and Disease in 3D Culture

EMBO | EMBL Symposium – Heidelberg, 10-13 September 2018
Meeting report by Veronica Foletto

Following the huge success of the 2016 symposium ‘Organoids: Modelling Organ Development and Disease in 3D Culture’, Hans Clevers, Jürgen Knoblich, Melissa Little, and Esther Schnapp joined forces to organise a second such symposium this year. On the afternoon of 10 September, 460 scientists from all over the world gathered in the auditorium of the EMBL Advanced Training Centre (ATC) in Heidelberg.

Hans Clevers, a leading expert on organoids, welcomed everyone and led the opening session. The first keynote lecture was given by Jürgen Knoblich, who reported on progress in his lab using cerebral organoids to model the complexity of the human brain and, in particular, to study microcephaly. The subsequent talks showed how organoids derived from different tissues provide useful models for the recapitulation of certain diseases such as Helicobacter pylori infection and secretion of the VacA toxin in the stomach, as discussed by Xuebiao Yao or models of early development, with Nicolas Rivron introducing the blastoid: a type of organoid similar to an early embryo, which can be used to study developmental processes in 3D.

The second day began early with an interesting ‘Meet the Editors’ session, in which scientists had the chance to talk directly to editors working for many scientific publishers (Springer, Nature, The Company of Biologists, Wiley, Cell Press and EMBO press) and to understand their vision.

Afterwards, Meritxell Huch chaired the session ‘Stem Cells and Development’, in which scientists presented advancements in the use of cerebral (Wieland Huttner) and pancreatic (Anne Grapin-Botton) organoids for deciphering cellular mechanisms during human development, and of gastruloids for studying the patterning of the antero-posterior axis (Denis Duboule). Near the end of the session, Bon-Kyoung Koo described how to efficiently use CRISPR technology to perform genetic studies in intestinal organoids. The session ended with a series of 2-minute flash talks, after which networking and interactions were encouraged during lunch, where there was an opportunity to meet the day’s speakers.

The beautiful helices of the ATC then provided the venue for the first poster session, where around 90 presenters had the chance to discuss their research with fellow scientists, editors, and a scientific evaluating committee. It was absolutely inspiring to see how many people work on organoid research!

The afternoon session, ‘Organoids from tissue stem cells’, included talks on organoids derived from taste stem cells (Peihua Jiang), cochlear cells (Albert Edge), and intestinal cells (Hans Clevers). Madeline Lancaster explored the possibility of studying differentiated human cerebral organoids which self-assemble in the stereotypic organisation of the early human embryonic brain and have functional motor-neuronal circuits.

Among this ‘zoo of organoids’ as humorously defined by Jürgen Knoblich there was room for organoids derived from snake venom glands (Yorick Post): the organoid toolbox seems to be extendable to non-mammalian cultures as well!

On Wednesday morning, James Wells introduced the session ‘Recreating organs from pluripotent stem cells’. This addressed cell fate decisions in the developing mouse thyroid gland or lung (Sabine Costagliola), the human lung (Jason Spence and Hans-Willem Snoeck), the human salivary gland (Cecilia Rocchi), and the human forebrain (Flora Vaccarino), studied primarily through single-cell transcriptome and enhancer analyses. Finally, it was the turn of Mathew Garnett, who started by showing that the worldwide number of new cases of cancer each year is around twice the population of Switzerland.

Interested in using precision organoid models to study cancer and patients’ responses to treatment, Garnett is now contributing to the development of the Human Cancer Models Initiative. Its goal is to create a new generation of molecularly annotated cancer models, which will be widely beneficial to the scientific community.

After the second poster session, there were talks on ‘Organoids and disease modelling’, introduced by Anne Grapin-Botton. Among the topics covered were the use of 3D organoids to model liver regeneration and disease (Meritxell Huch), and to study cancers of the bladder (Michael Shen), pancreas (David Tuveson), breast (Martin Jechlinger), and colon (Henner Farin).

The day ended beautifully with the conference dinner in the EMBL canteen and the delightful live music that brought together the diverse group of researchers once again.

The final day of the conference was dedicated to ‘Cells and materials in regenerative medicine’. Matthias Lutolf discussed some of the ongoing efforts in his research group to develop next-generation organoids through tissue engineering. Meritxell Cutrona reported advances in nanoparticle tracking in 3D structures, which is particularly useful for drug delivery. Lakmali Atapattu described 3D bioprinting of tumoroids. Henrik Renner presented a high throughput-compatible workflow for the generation, culture, and optical analysis of neural human organoids. Rob Coppes and Melissa Little reported on promising progress in improving cancer treatment, using glandular and kidney organoids, respectively. James Wells gave a talk on the applications of gastrointestinal organoids, concluding with some food for thought for the audience: “It is better to collaborate, than to compete.”

The Symposium ended with the poster prizes, sponsored by EMBO Reports, EMBO Molecular Medicine, and Sartorius. Personally, I found these four days extremely stimulating, full of opportunities for interaction and discussion. I believe most of my fellow researchers got the same feeling: 3D organoid systems are revolutionising molecular biology and driving the development of better clinical therapies, and we are all contributing to this revolution.

What will we be able to achieve with organoids in two years’ time?

Stay tuned, the meeting will be back in 2020!


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