Invited Speakers | Track 2

FROM GENES TO ORGANISMS
‘Genome regulation: how tissues and organisms form and survive’

Effie Apostolou

Assistent Professor at UMC Weill Cornell Medicine, USA – Department of Medicine

Effie Apostolou studied Biology in the Aristotle University of Thesaloniki in Greece (1998-2003). She did her PhD studies in Dimitris Thanos lab in Athens on mechanisms that regulate stochastic gene expression upon virus induction (Apostolou and Thanos, Cell 2008). In 2009 she joined Konrad Hochedlinger lab in MGH and Harvard Stem Cell institute in Boston to unravel epigenetic mechanisms that drive somatic cell reprograming to iPSCs (Apostolou*, Ferarri* et al, Cell Stem Cell 2013; Stadtfeld*, Apostolou* et al, Nature 2010; Stadtfeld*, Apostolou* et al, Nat. Gen. 2012).

In 2014, Effie Apostolou moved in NYC to Weill Cornell Medicine to establish her own group. Their main focus is to understand the role of transcription factors and chromatin organization in the maintenance or transition of cell fate, using somatic cell reprogramming and embryonic stem cell as a study systems. They have recently demonstrated that selected retention of transcription factors and chromatin marks on the mitotic chromatin is important for propagation of stem cell identity after cell division (Liu et al, Cell Reports 2017). They have also shown that transcription factors, such as KLF4, play important roles in the organization and transcriptional regulation of 3D enhancer hubs (Di Giammartino et al, Nature Cell Biology 2019). To address these questions, they are utilizing and implementing tools for genetic and epigenetic engineering as well as genome-wide chromatin assays, including ChIP-seq, ATAC-seq, 4C-seq, HiChIP and HiC.

Effie Apostolou has received several awards, including Jane Coffins Child Foundation and EMBO postdoctoral fellowships and NIH Director’s New Innovator award at 2015 as well as the Raymond and Beverly Sackler Research Scholar endowed position at 2018. Read more

Abstract
Mapping cell fate decisions in four dimensions

Every time that a cell divides “decides” whether it will maintain its identity (selfrenewal) or give rise to a new cell type, e.g. during differentiation, reprogramming or transformation. In my group, we study the interplay between transcription and epigenetic factors with 3D chromatin topology and their roles in cell fate decisions. In this talk, I will mostly focus on the mechanisms that ensure self-renewal, and specifically how cell type-defining features that are drastically perturbed during mitosis, are faithfully reestablished in the daughter cells upon G1 entry. We recently characterized at a genome-wide scale the dynamic transcriptional and architectural resetting of mouse pluripotent stem cells (PSCs) upon mitotic exit. We captured distinct waves of transcriptional reactivation with rapid induction of stem cell genes and transient activation of lineage-specific genes. Topological reorganization at different hierarchical levels also occurred in an asynchronous manner and showed partial coordination with transcriptional resetting. Globally, rapid transcriptional and architectural resetting associated with mitotic retention of H3K27 acetylation, supporting a bookmarking function. Indeed, mitotic depletion of H3K27ac impaired the early reactivation of bookmarked, stem cell-associated genes. However, 3D chromatin reorganization remained largely unaffected, suggesting these processes are driven by distinct forces upon mitotic exit. I will discuss the impact of this study and critical open questions in the field.

Hans Clevers (1957)

Professor at research institute Hubrecht Institute – Developmental Biology & Stem Cell Research

Hans Clevers obtained his MD degree in 1984 and his PhD degree in 1985 from the University Utrecht, the Netherlands. His postdoctoral work (1986-1989) was done with Cox Terhorst at the Dana-Farber Cancer Institute of the Harvard University, Boston, USA.

From 1991-2002 Hans Clevers was Professor in Immunology at the University Utrecht and, since 2002, Professor in Molecular Genetics. From 2002-2012 he was director of the Hubrecht Institute in Utrecht. From 2012-2015 he was President of the Royal Netherlands Academy of Arts and Sciences (KNAW). From 2015 – June 2019 he was Director Research of the Princess Maxima Center for pediatric oncology. He continues to run his lab in the Hubrecht Institute.

Throughout his career, he has worked on the role of Wnt signalling in stem cells and cancer. His discoveries include TCF as the nuclear Wnt effector, the role of Wnt in adult stem cell biology and of Wnt pathway mutations in colon cancer, Lgr5 as a marker of multiple novel types of adult stem cells and as receptor for the Wnt-amplifying R-spondins, and –finally- a method to grow ever-expanding mini-organs (‘organoids’) from Lgr5 stem cells derived from a range of healthy or diseased human tissues. This has led to over 600 publications and >70,000 citations.

Hans Clevers is member of the Royal Netherlands Academy of Arts and Sciences (2000), of the American Academy of Arts and Sciences (2012) and the National Academy of Sciences of the USA (2014), the Academie des Sciences (2016) and the Orden pour le Merite der Wisschschaften und Kuenste (2017).

He is the recipient of multiple awards, including the Dutch Spinoza Award in 2001, the Swiss Louis Jeantet Prize in 2004, the German Meyenburg Cancer Research Award in 2008, the German Ernst Jung-Preis für Medizin in 2011, the French Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize, the Heineken Prize (2012), the Breakthrough Prize in Life Sciences (2013), the 2015 ISSCR McEwen Award for Innovation and the Academy Professor Prize (2015), and the Körber European Science Prize (2016).

He is Chevalier de la Legion d’Honneur since 2005 and Knight in the Order of the Netherlands Lion since 2012. Read more

Abstract
Stem cell-based organoids in human disease

Stem cells are the foundation of all mammalian life. They come in two flavors. Embryonic stem cells are briefly present in the early human or mouse embryo, a few days after fertilization. These stem cells can be grown indefinitely in the lab and have the potential to build each and every tissue in our body. ES cells hold great promise in the field of regenerative medicine. Adult stem cells. Every organ in our body harbors its own dedicated stem cells. These adult stem cells replace tissue that is lost due to wear and tear, trauma and disease. Adult stem cells can only produce the tissue in which they reside. The adult stem cells allow us to live 80-90 years, but this comes at a cost: they easily turn into cancer. Both types of stem cells can be used to establish ‘organoids’, 3D structures established in a dish, that recapitulate many aspects of the original organ -including its diseases.