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Imaging of Pluripotency in Systems Biology

English title Imaging of Pluripotency in Systems Biology
Applicant Pantazis Periklis
Number 144048
Funding scheme Project funding (Div. I-III)
Research institution Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Embryology, Developmental Biology
Start/End 01.07.2013 - 30.06.2016
Approved amount 471'500.00
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Keywords (5)

photoactivation; transcription factor kinetics; embryonic stem cells; quantitative imaging; mouse embryo development

Lay Summary (German)

Lead
Wie früh werden Entscheidungen in der Etablierung der Zellidentitäten im Säugetierembryo getroffen? Es ist vorgeschlagen worden, dass die stochastische Position/Polarität von Zellen im 16-Zell-Embryo die Entscheidung beeinflusst, ob entweder die pluripotente Zelllinie oder die extraembryonale Zelllinie etabliert wird. Im Gegensatz zu dem stochastischen Modell haben einige Studien einen vermeintlichen Unterschied im Potenzial der einzelnen Blastomere vor dem 16-Zell-Embryo festgestellt.
Lay summary
Inhalt und Ziel des Forschungsprojekts
Mitte Hilfe eines nicht-invasiven, quantitativen in-vivo-Bildgebungsverfahrens, welches das kinetische Verhalten des Transkriptionsfaktors Oct4 in der Präimplantationsentwicklung des Mausembryos darstellt, haben wir festgestellt, dass die Oct4 Kinetik die Zelllinienetablierung im frühen Mausembryo vorhersagen kann. In diesem Forschungsprojekt werden wir die molekulare Natur dieses kinetischen Oct4 Verhaltens, das die Etablierung der ersten spezialisierten Zellen im lebenden Mausembryo zu steuern scheint, untersuchen. Aufbauend auf unseren bisherigen Ergebnissen werden wir die Hypothese, dass das kinetische Verhalten von Transkriptionsfaktoren einen allgemeinen Mechanismus zur Erlangung von Zellheterogenität und zur Etablierung der Musterbildung im Mausembryo darstellt, durch die systematische Messung der kinetischen Parameter der wichtigsten Transkriptionsfaktoren, die für die Präimplantationsentwicklung essentiell sind, prüfen. Darüberhinaus werden wir analysieren, ob man mit Hilfe der Kinetik von Transkriptionsfaktoren den pluripotenten Zustand in Stammzellen definieren kann. Dabei werden wir das Verhalten der Transkriptionsfaktorkinetik im Embryo mit embryonalen Stammzellen (ES-Zellen) vergleichen.

Wissenschaflticher und gesellschaftlicher Kontext des Forschungsprojekts
Das im Forschungsprojekt erworbene Wissen wird dazu beitragen, einige Kontroversen in der Zelllinienzuteilung im frühen Säugetierembryo zu beantworten (z.B. stochastische gegen vorgegebene Entstehung der Zellidentität). Darüberhinaus wird auf lange Sicht die zellbasierte Therapie in der regenerativen Medizin von unseren Erkenntnissen profitieren. Insbesondere wird das Verständnis der molekularen Regulierung des Ursprungs der Pluripotenz Anhaltspunkte für die Erzielung einer optimalen Umgebung zur Differenzierung pluripotenter Stammzellen in verschiedene spezialisierte Zelltypen geben. Die Beurteilung einer effizienten Reprogrammierung von somatischen Zellen in pluripotente Stamzellen (sogenannte iPSC) wird auch von unseren Erkenntnissen profitieren.

Keywords
mouse embryo development, quantitative imaging, transcription factor kinetics, photoactivation, embryonic stem cells
Direct link to Lay Summary Last update: 25.06.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Symmetry breaking in the early mammalian embryo: the case for quantitative single-cell imaging analysis
Welling Maaike, Ponti Aaron, Pantazis Periklis (2016), Symmetry breaking in the early mammalian embryo: the case for quantitative single-cell imaging analysis, in Molecular Human Reproduction, 22(3), 172.
Determination of the source of SHG verniers in zebrafish skeletal muscle
Dempsey William P, Hodas Nathan O, Ponti Aaron, Pantazis Periklis (2015), Determination of the source of SHG verniers in zebrafish skeletal muscle, in Scientific Reports, 5, 18119.
In vivo single-cell labeling by confined primed conversion
Dempsey William P, Georgieva Lada, Helbling Patrick M, Sonay Ali Y, Truong Thai V, Haffner Michel, Pantazis Periklis (2015), In vivo single-cell labeling by confined primed conversion, in Nature Methods, 12(7), 645.

Collaboration

Group / person Country
Types of collaboration
Hari Schroff, NIH United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Ulrich Nienhaus, KIT Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Eric Schreiter, HHMI Janelia Research Campus United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
68th Annual Meeting of the Japan Society of Cell Biology Talk given at a conference Symmetry breaking in the early mammalian embryo: the case for quantitative single-cell imaging 16.06.2016 Kyoto, Japan Pantazis Periklis;
16th European Light Microscopy Initiative (ELMI) Meeting Talk given at a conference Mapping single neuron morphology in vivo with confined primed conversion 27.05.2016 Debrecen, Hungary Pantazis Periklis; Qin Hanyu;
4th European Zebrafish Principle Investigator Meeting Talk given at a conference Mapping single neuron morphology in vivo with confined primed conversion 18.03.2016 Lisbon, Portugal Pantazis Periklis; Qin Hanyu;
7th Annual EFOR Meeting Talk given at a conference Mapping single neuron morphology in vivo with confined primed conversion 07.03.2016 Paris, France Pantazis Periklis;
Symposium “Seeing is Believing – Imaging the Processes of Life European Molecular Biology Laboratory (EMBL) Talk given at a conference Mapping single neurons in vivo with confined primed conversion 06.10.2015 Heidelberg, Germany Pantazis Periklis;
15th European Light Microscopy Initiative (ELMI) Meeting Talk given at a conference In vivo single cell labeling by confined primed conversion 19.05.2015 Barcelona, Spain Pantazis Periklis;
6th Strategic Conference of Zebrafish Investigators Talk given at a conference mapping single neuron morphology in vivo with confined primed conversion 19.01.2015 Asilomar, CA, United States of America Qin Hanyu; Pantazis Periklis;
Novartis Workshop “Using 3D cell cultures and organ printing in drug discovery – cells, biosensors and imaging technology” Talk given at a conference Advances in whole embryo imaging: a quantitative transition is underway 30.10.2014 Basel, Switzerland Pantazis Periklis;
Quantitative Single Cell Biology in Stem Cell Research Talk given at a conference Tracking pluripotency: advanced imaging tools for probing asymmetry in early mammalian embryos 10.10.2013 Munich, Germany Pantazis Periklis; Georgieva Lada;


Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) Chameleon proteins make individual cells visible Featured in 11 news outlets and scientific blogs among them: Bergman, F. (2015) “Chameleon proteins International 2015

Associated projects

Number Title Start Funding scheme
164087 Lightsheet Microscopy 01.06.2016 R'EQUIP

Abstract

There is a long-running controversy about how early cell fate decisions are made in the developing mammalian embryo. In particular, it is controversial when the first events that can predict the establishment of the pluripotentand extra-embryonic lineages in the blastocyst of the pre-implantation embryo occur. It has long been proposed that the position and polarity of cells at the 16- to 32-cell stage embryo influence their decision to either give rise to the pluripotent cell lineage that eventually contributes to the inner cell mass (ICM), comprising the primitive endoderm (PE) and the epiblast (EPI), or the extra-embryonic trophectoderm (TE) surrounding the blastocoel. The positioning of cells in the embryo at this developmental stage could be largely the result of random events, making this a stochastic model of cell lineage allocation. Contrary to such a stochastic model, some studies have detected putative differences in the lineage potential of individual blastomeres before compaction, indicating that the first cell fatedecisions may occur as early as at the 4-cell stage. Using a non-invasive, quantitative in vivo imaging assay to study the kinetic behavior of Oct4, a key transcription factor (TF) controlling pre-implantation development in the mouse embryo, we identified Oct4 kinetics as a predictive measure of cell lineage patterning in the early mouse embryo.Here, we will investigate the molecular nature of this kinetic behavior that controls the development of the first specialized cells in living mouse embryos. Building upon our previous results we will test the hypothesis that TF kinetic behaviors may represent a general mechanism to establish heterogeneities and control lineage patterning in the mouse embryo by systematically measuring the kinetic parameters of the main TFs essential for pre-implantation development. Finally, we will further determine if TF kinetics are a unique mark that defines the pluripotent state by comparing TF kinetics in the embryo to embryonic stem (ES) cells.
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