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PhD thesis defense by Abhishek S. Prayagpour

Published on July 19, 2017

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Pluripotent stem cells in Mammals


We explore the mechanisms of self-renewal and pluripotency in mouse, rabbit, macaque monkey, and human embryonic stem cells. We identified novel genes involved in the maintenance of the undifferentiated state and in early commitment towards mesodermal and endodermal lineages. Another aspect of our work focuses on the regulation of the cell cycle, which shows unusual characteristics in pluripotent stem cells. In parallel, we explore ground state pluripotency in the rabbit and primate pre-implantation embryos. Our goal is to create rabbit and macaque ES cells capable of colonizing the developing embryo, suitable for the generation of somatic and germline chimaeras.

Pierre Savatier

DR2 INSERM, Team leader. He obtained his PhD from the University of Lyon in 1986. He joined INSERM in 2004 as an AVENIR team leader, and the same year he was awarded the “Coup d’Elan pour la recherche” from the Bettencourt Foundation. His team participates in two laboratory of excellence (LabEx): DEVweCAN and CORTEX. His is responsible for PrimaStem, a technological platform specialized in pluripotent stem cells in primates. PrimaStem participates ...

Irène Aksoy-Marcy

Postdoc. She obtained her PhD from the University of Lyon in 2008. After a 5-year postdoc at the Genome Institute of Singapore, where she studied different aspects of somatic cell reprogramming, she joined the Savatier team in 2013 to work on pluripotency in non-human primates. She studies the transcriptome of the macaque pre-implantation, and reprograms ES cell lines suitable for the generation of somatic chimaeras in the rhesus macaque.

Dr Nathalie Beaujean

DR2 INRA. She earned her PhD in Paris, in 2001, and then worked as a post-doc at the Roslin Institute (Scotland). She joined INRA in 2003, at Jouy-en-Josas, to develop studies on chromatin remodeling  during  preimplantation development , mainly in murine and rabbit/bovine species. She is very experienced in the analysis of epigenetic reprogramming by powerful image analysis tools.

Since her arrival at SBRI her project is to ...

Pierre-Yves Bourillot

CR1 CNRS. He obtained his PhD from the University of Lyon in 1997. After a 3-year postdoc at the University of Cambridge (UK), he joined the Savatier team in 2000. He studies LIF/STAT3 signalling in mouse and human ES cells. In collaboration with Hongwei Chen, he reprogrammed human ES cells to ground-like state of pluripotency. He also studies the role of long non-coding RNAs in ground state pluripotency.

Antoine Cadiou

Edwige Delahaye

Fabrice Gonnot

He joined the Savatier team to study the regulation of the embryonic stem cells (ES) cell cycle by transcription factors of the core pluripotency network.

Arnaud Hochard

Research engineer (CDD). He obtained his PhD from the University of Rennes in 2012, and joined the Savatier team in 2013. He develops assisted reproductive technology (ART) and somatic cell reprogramming in non-human primates.

Lucas Medjani

Intern. He joined the Savatier team in 2014 for an internship at the Ecole Pratique des Hautes Etudes. He develops the technique of single-cell qRT-PCR on rabbit pre-implantation embryos.

Anaïs Moulin

Research engineer (CDD). She joined the Savatier team in 2012 for an internship at the Ecole Pratique des Hautes Etudes. She graduated in December 2014 and now works as a research engineer. She develops novel ES cell lines suitable for the generation of somatic chimaeras in rabbits.

Claire Santamaria
PhD Student. She joined the Savatier's team in February 2015 to work on LIF/STAT3 signalling and pluripotency in human.
Selected Publications of Team members :
Aksoy I, Utami KH, Winata CL, Hillmer AM, Rouam SL, Briault S, Davila S, Stanton LW, Cacheux V. (2017) Personalized genome sequencing coupled with iPSC technology identifies GTDC1 as a gene involved in neurodevelopmental disorders Hum Mol Genet. 2017 Jan 15;26(2):367-382
Aksoy I, Marcy G, Chen J, Divakar U, Kumar V, John-Sanchez D, Rahmani M, Buckley NJ, Stanton LW. (2016) A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification. Apr;34(4):860-72.
Afanassieff M, Osteil P, Savatier P. (2015) Generation of embryonic stem cells in rabbits. Methods Mol Biol. 1357:49-66
Afanassieff M, Tapponnier Y, Savatier P (2014) Generation of Induced Pluripotent Stem Cells in Rabbits. Methods Mol Biol. [Epub ahead of print]
Aksoy I, Giudice V, Delahaye E, Wianny F, Aubry M, Mure M, Chen J, Jauch R, Bogu GK, Nolden T, Himmelbauer H, Xavier Doss M, Sachinidis A, Schulz H, Hummel O, Martinelli P, Hübner N, Stanton LW, Real FX, Bourillot PY, Savatier P. (2014) Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells. Nat Comm, 5:3719
Coronado D, Godet M, Bourillot PY, Tapponnier Y, Bernat A, Petit M, Afanassieff M, Markossian S, Malashicheva A, Iacone R., Anastassiadis K, Savatier P (2013) A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency. Stem Cell Res 10(1): 118-31 download
Osteil P, Tapponnier Y, Markossian S, Godet M, Schmaltz-Panneau B, Jouneau L, Cabau C, Joly T, Blachère T, Gozca E, Bernat A, Yerle M, Acloque H, Hidot S, Bözse Z, Duranthon V, Savatier P, Afanassieff M (2013) Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naïve pluripotency Biology Open 2:613-628 download
Dolmazon V, Alenina N, Markossian S, Mancip J, van de Vrede Y, Fontaine E, Dehay C, Kennedy H, Bader M, Savatier P, Bernat A (2011) Forced expression of Lmx1b enhances differentiation of mouse ES cells into serotonergic neurons. Stem Cells Dev, 2011, 20:301-311
Bourillot PY, Savatier P. (2010) Krüppel-like transcription factors and control of pluripotency. BMC Biol. 27(8): 125 Review. download
Niu Y, Yu Y, Bernat A, Yang S, He X, Guo X, Chen D, Chen Y, Ji S, Si W, Tan T, Wei Q, Wang H, Shi L, Afanassieff M, *Savatier P, *Zhou Q, *Ji W (2010) Transgenic rhesus monkeys produced by gene transfer into early cleavage stage embryos using a simian immunodeficiency virus-based vector. Proc Natl Acad Sci USA, 107:17663-7
Bourillot PY, Aksoy I, Schreiber V, Wianny F, Schulz H, Hummel O, Hubner N, Savatier P. (2009) Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and endoderm differentiation in cooperation with nanog Stem Cell 27(8): 1760-1771 download
Schulz H et al (2009) Functional Genomics in Embryonic Stem Cells Consortium. The FunGenES database: a genomics resource for mouse embryonic stem cell differentiation. PloS One, 4(9): e6804. download
Marchand M, Schröder I, Markossian S, Skoudy A. Nègre D. Cosset FL, Real FX, Wobus AM, Savatier P (2009) Mouse ES cells overexpressing the transcription factor NeuroD1 show increased differentiation towards endocrine lineages Int. J. Dev. Biol. 53:569-578. download
Wianny F, Bernat A, Huissoud C, Marcy G, Markossian S, Cortay V, Giroud P, Leviel V, Kennedy H, Savatier P, Dehay C (2008) Derivation and cloning of a Novel Rhesus ES cell line stably expressing Tau-GFP. Stem Cells. 2008 26(6):1444-1453 download
Aksoy I, Sakabedoyan C, Bourillot PY, Malashicheva AB, Mancip J, Knoblauch K, Afanassieff M, Savatier P (2007) Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases pim-1 and pim-3. Stem Cells 25(12):2996-3004 download
Fluckiger AC, Marcy G, Marchand M, Negre D, Cosset FL, Mitalipov S, Wolf D, Savatier P, Dehay C (2006) Cell cycle features of Primate Embryonic Stem Cells Stem Cells 24(3):547-556 download
Lukaszewicz A, Savatier P, Cortay V, Giroud P, Huissoud C, Berland M, Kennedy H, Dehay C (2005) G1 phase regulation, Area-Specific cell cycle control, and Cytoarchitectonics in the Primate Cortex. Neuron, 2005, 47:353-364 download
Jirmanova L, Afanassieff M, Gobert-Gosse S, Markossian S, Savatier P (2002) Differential contributions of ERK and PI3-kinase to the regulation of cyclin D1 expression and to the control of the G1/S transition in mouse embryonic stem cells. Oncogene 21:5515-28 download
Burdon T, Smith AG, Savatier P (2002) Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 12:432-8 download