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Regulation of stem cell plasticity in Hydra

English title Regulation of stem cell plasticity in Hydra
Applicant Galliot Brigitte
Number 149630
Funding scheme Project funding (Div. I-III)
Research institution Département de Génétique et Evolution Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Embryology, Developmental Biology
Start/End 01.10.2013 - 30.09.2016
Approved amount 610'000.00
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All Disciplines (3)

Discipline
Embryology, Developmental Biology
Molecular Biology
Cellular Biology, Cytology

Keywords (8)

adult stem cells; Hydra regeneration; cellular plasticity; wound healing; ROS signaling; MAPK signaling; RNAseq transcriptomes; resistance to cell death

Lay Summary (French)

Lead
Comprendre les mécanismes de la plasticité cellulaire et de la régénération en utilisant le modèle de l’Hydre d’eau douce.
Lay summary

L’Hydre est un petit animal qui repousse tout partie manquante à la suite d’une amputation, la tête du côté apical dotée d’un système nerveux dense, et le disque basal, plus simple, de l’autre côté. Grâce aux nouveaux outils récemment développés dans le laboratoire, la cytométrie en flux pour étudier les variations du cycle cellulaire des différentes populations de cellules souches, et le séquençage de nouvelle génération pour le contrôle génétique de la régénération, nous proposons d’analyser dans ce projet quatre aspects de la régénération:

1) les signaux immédiatement produits au niveau de la blessure, pour comprendre comment ces signaux induisent les programmes de régénération,

2) les caractères spécifiques des programmes qui permettent la régénération de la tête ou du pied, mais aussi les variations du programme de régénération de la tête en fonction du niveau de bisection le long du corps,

3) la plasticité des cellules souches épithéliales après bisection, lorsque le tissu gastrique devient un centre organisateur, ou après élimination des cellules souche interstitielles,

4) les régulateurs de la résistance à la mort cellulaire des cellules souches épithéliales. Les gènes candidats seront également testés dans les cellules de mammifères.

Les résultats attendus devraient nous aider à comprendre d’une part l’impact des conditions homéostatiques qui précèdent l’amputation sur l’initiation d’un programme de régénération, d’autre part le rôle de la plasticité cellulaire dans un programme de régénération. Finalement la compréhension des mécanismes de résistance à la mort cellulaire est un élément essentiel de la lutte contre la récurrence du cancer.

 

Direct link to Lay Summary Last update: 23.10.2013

Lay Summary (English)

Lead
Understanding cell plasticity and regenerative programs in the freshwater Hydra
Lay summary

Our laboratory is using the Hydra model system to investigate the mechanisms of regeneration as this little animal easily regrows any missing part after bisection, on the apical side the rather complex head region, and on the other side the basal disk. Thanks to the tools we recently generated, namely flow cytometry to study the cell cycling behaviors of the different stem cell populations in Hydra, and Next Generation Sequencing to investigate the genetic control of regeneration, we propose now to investigate four aspects of regeneration in Hydra,

1) the signals immediately produced upon injury, which activate or modulate the regeneration programs,

2) the specific features of the head and foot regenerative programs, but also the variations in the head regenerative program when initiated from distinct levels along the body column,

3) the changes undergone by the epithelial stem cells when the digestive tissue acquires an organizing activity after bisection, or when the interstitial cells are eliminated,

4) the molecular properties of the epithelial stem cells that allow them to resist to cell death. The genes that will be identified as candidate regulators of cell death resistance in the Hydra epithelial stem cells will also be tested in mammalian cells.

The results obtained in this study should help understand how the control of cell plasticity allows the emergence of regenerative programs in animals, but also how the homeostatic conditions that precede bisection impact on the choice between several developmental programs in a relatively complex organism as Hydra. Finally understanding the mechanisms of cell death resistance is a major task to face cancer recurrence.

 

Direct link to Lay Summary Last update: 23.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
An evolutionarily-conserved Wnt3/-catenin / Sp5 feedback loop module restricts head organizer in Hydra
VOGG Matthias, BECCARI Leo, IGLESIAS OLLE Laura, PERRUCHOUD Chrystelle, RAMPON Christine, VRIZ Sophie, WENGER Yvan, GALLIOT Brigitte (2018), An evolutionarily-conserved Wnt3/-catenin / Sp5 feedback loop module restricts head organizer in Hydra, in BioRXiv, 265785.
Hydra , a Model System for Deciphering the Mechanisms of Aging and Resistance to Aging
Schenkelaars Quentin, Tomczyk Szymon, Wenger Yvan, Ekundayo Kazadi, Girard Victor, Buzgariu Wanda, Austad Stephen, Galliot Brigitte (2018), Hydra , a Model System for Deciphering the Mechanisms of Aging and Resistance to Aging, in Ram Jeffrey (ed.), Elsevier, Cambridge, Massachusetts, US, 507-520.
Impact of cycling cells and cell cycle regulation on Hydra regeneration
Buzgariu Wanda, Wenger Yvan, Tcaciuc Nina, Catunda-Lemos Ana-Paula, Galliot Brigitte (2018), Impact of cycling cells and cell cycle regulation on Hydra regeneration, in Developmental Biology, 433(2), 240-253.
Non-developmental dimensions of adult regeneration in Hydra
Galliot Brigitte, Buzgariu Wanda, Schenkelaars Quentin, Wenger Yvan (2018), Non-developmental dimensions of adult regeneration in Hydra, in The International Journal of Developmental Biology, 62(6-7-8), 373-381.
Deficient autophagy drives aging in Hydra
Tomczyk Szymon, Schenkelaars Quentin, Suknovic Nenad, Wenger Yvan, Ekundayo Kazadi, Buzgariu Wanda, Bauer Christoph, Fischer Kathleen, Austad Stephen, Galliot Brigitte (2017), Deficient autophagy drives aging in Hydra, in BioRXiv, 236638.
Hydra, a model system for deciphering the mechanisms of aging and resistance to aging
Schenkelaars Quentin, TomczykSzymon, WengerYvan, EkundayoKazadi, GirardVictor, BuzgariuWanda, AustadStephen, GalliotBrigitte (2017), Hydra, a model system for deciphering the mechanisms of aging and resistance to aging, in BioRXiv, 155804.
Trends in tissue repair and regeneration
Galliot Brigitte, Crescenzi Marco, Jacinto Antonio, Tajbakhsh Shahragim (2017), Trends in tissue repair and regeneration, in Development, 144(3), 357-364.
Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells
Wenger Y., Buzgariu W., Galliot B. (2016), Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells, in Philosophical Transactions of the Royal Society B: Biological Sciences, (1685), 20150040-20150040.
Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells
Wenger Y., Buzgariu W., Galliot B. (2016), Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells, in Philosophical Transactions of the Royal Society B: Biological Sciences, 371(1685), 20150040-20150040.
How Somatic Adult Tissues Develop Organizer Activity
Vogg Matthias C., Wenger Yvan, Galliot Brigitte (2016), How Somatic Adult Tissues Develop Organizer Activity, in Paul Wassarman (ed.), Elsevier, New York, USA, 391-414.
How Somatic Adult Tissues Develop Organizer Activity
Vogg Matthias C., Wenger Yvan, Galliot Brigitte (2016), How Somatic Adult Tissues Develop Organizer Activity, in Current Topics in Developmental Biology, 96, 391-414.
A dynamic architecture of life
Rubin Beatrix, Brockes Jeremy, Galliot Brigitte, Grossniklaus Ueli, Lobo Daniel, Mainardi Marco, Mirouze Marie, Prochiantz Alain, Steger Angelika (2015), A dynamic architecture of life, in F1000 Research, 4, 1288.
Multi-functionality and plasticity characterize epithelial cells in Hydra
Buzgariu W, Al Haddad S, Tomczyk S, Wenger Y, Galliot B (2015), Multi-functionality and plasticity characterize epithelial cells in Hydra, in Tissue Barriers, 3(4), e1068908-e1068908.
The TALE face of Hox proteins in animal evolution
Merabet Samir, Galliot Brigitte (2015), The TALE face of Hox proteins in animal evolution, in Frontiers in Genetics, 6(267), 1.
Cell death: a program to regenerate
Vriz Sophie, Reiter Silke, Galliot Brigitte (2014), Cell death: a program to regenerate, in Current Topics in Developmental Biology, 108, 121-151.
Hydra, a powerful model for aging studies
Tomczyk Szymon, Fischer Kathleen, Austad Steven, Galliot Brigitte (2014), Hydra, a powerful model for aging studies, in Invertebrate Reproduction & Development, 59(sup1), 11-16.
Injury-induced immune responses in Hydra
Wenger Yvan, Buzgariu Wanda, Reiter Silke, Galliot Brigitte (2014), Injury-induced immune responses in Hydra, in Seminars in Immunology, 26(4), 277-294.
Mechanisms of regeneration. Preface.
Galliot Brigitte (2014), Mechanisms of regeneration. Preface., in Current Topics in Developmental Biology, 108, xiii-xviii.
Robust G2 pausing of adult stem cells in Hydra
Buzgariu Wanda, Crescenzi Marco, Galliot Brigitte (2014), Robust G2 pausing of adult stem cells in Hydra, in Differentiation, 87(1-2), 83-99.
Combining BrdU-labeling to detection of neuronal markers to monitor adult neurogenesis in Hydra
Buzgariu Wanda, Curchod Marie-Laure, Perruchoud Christelle, Galliot Brigitte, Combining BrdU-labeling to detection of neuronal markers to monitor adult neurogenesis in Hydra, in Methods in Molecular Biology.
Modern genomic tools reveal the structural and cellular diversity of cnidarian nervous systems
RentzschFabian, GalliotBrigitte, JulianoCelina, Modern genomic tools reveal the structural and cellular diversity of cnidarian nervous systems, in Current Opinion in Neurobiology, 56.

Datasets

HydrAtlas

Author Wenger, Yvan; Galliot, Brigitte
Publication date 01.06.2018
Persistent Identifier (PID) none at the moment
Repository Hydratlas.unige.ch
Abstract
We present here a transcriptome-wide characterization of spatial and cell-type specific expression patterns in non-regenerating animals, augmented with a comparison of transcript modulations during apical and basal regeneration after decapitation and mid-gastric bisection. The homeostatic and regeneration profiles of 25’637 Hydra transcripts are available on HydrAtlas (https://hydratlas.unige.ch), a web interface allowing a convenient access to the profiles of each transcript. Quantitative RNA-seq data were produced in several independent replicates (i) from slices dissected along the body column, (ii) from FACS-sorted cells of transgenic lines constitutively expressing GFP in one or the other stem cell populations, (iii) from the body column of animals having lost their ISCs after drug or heatshock treatment, (iv) from regenerating tips undergoing either head or foot regeneration at nine distinct time-points, from 30 minutes up to 48 hours post-amputation.

Collaboration

Group / person Country
Types of collaboration
Steve Austad/ University of Alabama at Birmingham - US United States of America (North America)
- Publication
Labo VRIZ / College de France France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
24th conference of the European Cell Death Organization, “Cell Death in Health and Disease” Poster ROS signaling and injury-induced cell death 26.09.2016 Barcelona, Spain Suknovic Nenad;
EMBO Conference The molecular and cellular basis of regeneration and tissue Poster STUDY OF THE RELATIONSHIP BETWEEN AGING, REGENERATION AND AUTOPHAGY BY COMPARING TWO DIFFERENT STRAINS OF HYDRA OLIGACTIS (CNIDARIA) 21.09.2016 Paestum (Saverno), Italy Schenkelaars Quentin;
EMBO Conference The molecular and cellular basis of regeneration and tissue Talk given at a conference Epithelial plasticity in Regenerating and Aging Hydra 20.09.2016 Paestum (Salerno), Italy Galliot Brigitte;
Cell symposia: Aging and Metabolism Poster Deficiency in epithelial autophagy leads to aging in Hydra 10.07.2016 Melia Sitges, Spain Tomczyk Szymon;
Embryology Course Marine Biology Laboratory Talk given at a conference Hydra a model system for regeneration and aging studies 01.07.2016 Woods Hole, MA, United States of America Galliot Brigitte;
The Stem Cell Niche 2016: Development & Disease 9th Copenhagen Bioscience Conference Talk given at a conference Epithelial plasticity in Regenerating and Aging Hydra 24.05.2016 Favrholm Campus in Hillerød-Copenhagen, Denmark Galliot Brigitte;
7th Annual meeting of the EFOR network Talk given at a conference Epithelial plasticity, a path to fitness, regeneration and slow aging 07.03.2016 Paris, France Galliot Brigitte;
Spongex meeting The origin of metazoans Talk given at a conference Loss of neurogenesis in Hydra, a path to proto-neuronal ages? 14.10.2015 Giens, France Galliot Brigitte;
23rd ECDO Conference on Cell Detah: Death Pathways and Beyond Poster Deficient autophagy drives aging in Hydra 07.10.2015 Centre de Convention d'Archamps, France Tomczyk Szymon;
23rd ECDO Conference on Cell Detah: Death Pathways and Beyond Poster ROS signaling and injury-induced cell death in Hydra 07.10.2015 Centre de Convention Archamps, France Suknovic Nenad;
Vriz/Galliot lab symposium Talk given at a conference Progress reports on regeneration mechanisms, ROS signaling, aging 06.10.2015 Geneva, Switzerland Suknovic Nenad; Galliot Brigitte; Tomczyk Szymon; Schenkelaars Quentin;
Jacques Mondo Conference Building, Repairing, and Evolving Biological Tissues Talk given at a conference Epithelial plasticity in homeostatic, regenerating and aging Hydra 13.09.2015 Roscoff, France Galliot Brigitte;
Systems biology of the brain CUSO Staromics PhD-program Workshop Talk given at a conference The Hydra nervous system, maintenance, regeneration and loss upon aging 24.08.2015 Fribourg, Switzerland Galliot Brigitte;
Comparative Biology of Tissue Re pair, Regeneration, and Aging Symposium Talk given at a conference Deficiency in epithelial plasticity drives loss of regeneration and aging in Hydra 26.06.2015 Bar-Harbor, Maine, United States of America Galliot Brigitte;
Regeneration Course Mount Desert Institute Biological Laboratory Talk given at a conference Hydra a model system for deciphering regenerative mechanisms 23.06.2015 Bar-Harbor, Maine USA, United States of America Galliot Brigitte;
seminar at the Department of Fundamental Neurosciences University of Lausanne Individual talk Cnidaria and the Emergence of Neurogenesis 12.06.2015 Lausanne, Switzerland Galliot Brigitte;
Synapses and Brains Peking University, Beijing, China Talk given at a conference Resistance to the loss of neurogenesis underlies high regenerative capabilities and slow aging in Hydra 21.05.2015 Beijing, China Galliot Brigitte;
Wellcome Trust Scientific Conferences The Biology of Regenerative Medicines Talk given at a conference Resistance of epithelial cells to the loss of neurogenesis in Hydra 24.04.2015 Cambridge, Great Britain and Northern Ireland Galliot Brigitte;
Neuro-PSI Lecture, Neurosciences Paris Saclay Institute Individual talk Hydra, a model of epithelial plasticity 30.01.2015 Gif-sur-Yvette, France Galliot Brigitte;
seminar at National University of Ireland Galway Individual talk Hydra, a model of epithelial plasticity 26.11.2014 Gallway, Ireland Galliot Brigitte;
seminar at Center for Integrative Genomics, Unil Individual talk Hydra, a model of epithelial plasticity 20.10.2014 Lausanne, Switzerland Galliot Brigitte;
22nd European Cell Death Organization ECDO conference Talk given at a conference Cell death, a program to regenerate in Hydra 04.10.2014 Hersonissos, Crete, Greece Galliot Brigitte;
seminar at Department of Cell Physiology and Metabolism, Medical School of Geneva Individual talk How to translate injury into a 3D regeneration process? 24.09.2014 Geneva, Switzerland Galliot Brigitte;
EMBO conference on Tissue Repair and Regeneration 2014 Talk given at a conference Injury-induced signals and innate immunity in regenerating Hydra 07.09.2014 Sant Feliu de Guixol, Spain Galliot Brigitte;
Euro Evo-Devo 2014 Talk given at a conference INJURY-INDUCED CELL DEATH 25.07.2014 Vienna, Austria Galliot Brigitte;
Embryology Course Marine Biology Laboratory Talk given at a conference Hydra a model system for tissular plasticity 02.07.2014 Woods Hole, MA, USA, United States of America Galliot Brigitte;
10th Annual meeting of the Swiss Stem Cell Network Talk given at a conference  Ageing and Regeneration:two faces of the same stem cells 04.06.2014 Geneva, Switzerland Galliot Brigitte;
A Dynamic Architecture of Life Workshop Rome Talk given at a conference Plasticity of homeostasis and regeneration in Hydra 26.05.2014 Accademia Nazionale dei Lincei, Roma, Italy Galliot Brigitte;
European and Swiss Congress of Internal Medicine (ESCIM) Talk given at a conference Ageing: from Hydra to humans 14.05.2014 Geneva, Switzerland Galliot Brigitte;
seminar at Institute of Cell Biology, University of Bern Individual talk How to translate injury into a 3D reconstruction program? 12.05.2014 Bern, Switzerland Galliot Brigitte;
Seminar at Institut de Génomique Fonctionnelle, ENS Lyon Individual talk Hydra a model system for stem cells, regeneration and aging studies 17.03.2014 Lyon, France Galliot Brigitte;
PhD retreat of the PhD program of Geneva in Life Sciences Talk given at a conference Aging or no aging in Hydra, a matter of stem cells? 23.10.2013 Biel, Switzerland Tomczyk Szymon;
invitation to give a seminar Individual talk Hydra a model system for regeneration and aging studies 17.10.2013 Stockholm, Sweden Galliot Brigitte;
Cold Spring Harbor meeting on Cell Death Poster MITOCHONDRIAL ROS TRIGGER INJURY-INDUCED CELL DEATH IN HEAD REGENERATING HYDRA 08.10.2013 Cold Spring Harbor, NY, US, United States of America Galliot Brigitte;


Self-organised

Title Date Place
23rd ECDO Euroconference on Cell Death: Death Pathways and Beyond 07.10.2015 Convention center Archamps, France
Vriz/Galliot lab retreat 31.03.2014 Lyon, France

Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) Rencontre avec Brigitte Galliot CQFD - Radio la 1ère - Avis d'experts Western Switzerland 2016
Talks/events/exhibitions Exposé: Vieillissement et Régénération International 2015
New media (web, blogs, podcasts, news feeds etc.) L’hydre modifie son programme génétique CQFD la 1ère - Avis d'experts Western Switzerland 2015

Associated projects

Number Title Start Funding scheme
169930 Cellular and Developmental Plasticity in Regenerating and Aging Hydra 01.11.2016 Project funding (Div. I-III)
130337 Genetic Regulation of Cell and Developmental Plasticity in Hydra 01.07.2010 Project funding (Div. I-III)

Abstract

Research performed on animal species able to regenerate appendages, organs or tissues in adulthood have demonstrated the potential of adult stem cells (ASCs) and/or differentiated cells to restaure missing or injured structures. We also know since 2006 that differentiated cells can reactivate their stem cell potential, offering potent tools for regenerative medicine. However there is a need to fully understand the mechanisms that maintain ASCs or promote their differentiation, and those that lead differentiated cells to spontaneously dedifferentiate or transdifferentiate. The freshwater cnidarian polyp Hydra provides a unique model system to investigate the relationships between stemness, cell plasticity, regenerative potential and aging. Indeed Hydra maintains its body shape through continuous cell renewal, can regenerate any missing body part, and shows low senescence. These properties rely on three distinct stem cell populations that cannot replace each other, ectodermal epithelial and endodermal epithelial, both unipotent, and interstitial, multipotent. Recent work from our laboratory showed that interstitial cells are highly sensitive to cell death whereas the epithelial cells, predominantly in G2, are cell death resistant. Interestingly the elimination of the interstitial cells is compatible not only with animal survival but also with the maintenance of regeneration and budding. In this proposal we wish to combine Next Generation Sequencing and transgenic strategies to characterize the biochemical and genetic cascades that immediately after bisection promote the formation of an organizing activity in an adult gastric tissue, to evaluate the impact of epithelial cell death resistance and G2 pausing on regeneration. From these approaches, we expect to further characterize the role of injury-induced ROS signaling in wound healing and regeneration, and to identify novel regulators of physiological reprogramming, either when the animals regenerate or when they loose their interstitial cells. These candidates will be tested in mammalian contexts.
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