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  1. Article ; Online: Molecular versatility during pluripotency progression.

    Furlan, Giacomo / Huyghe, Aurélia / Combémorel, Noémie / Lavial, Fabrice

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 68

    Abstract: A challenge during development is to ensure lineage segregation while preserving plasticity. Using pluripotency progression as a paradigm, we review how developmental transitions are coordinated by redeployments, rather than global resettings, of ... ...

    Abstract A challenge during development is to ensure lineage segregation while preserving plasticity. Using pluripotency progression as a paradigm, we review how developmental transitions are coordinated by redeployments, rather than global resettings, of cellular components. We highlight how changes in response to extrinsic cues (FGF, WNT, Activin/Nodal, Netrin-1), context- and stoichiometry-dependent action of transcription factors (Oct4, Nanog) and reconfigurations of epigenetic regulators (enhancers, promoters, TrxG, PRC) may confer robustness to naïve to primed pluripotency transition. We propose the notion of Molecular Versatility to regroup mechanisms by which molecules are repurposed to exert different, sometimes opposite, functions in close stem cell configurations.
    MeSH term(s) Pluripotent Stem Cells ; Transcription Factors/genetics ; Cell Differentiation ; Nanog Homeobox Protein ; Octamer Transcription Factor-3
    Chemical Substances Transcription Factors ; Nanog Homeobox Protein ; Octamer Transcription Factor-3
    Language English
    Publishing date 2023-01-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-35775-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: m

    Collignon, Evelyne / Cho, Brandon / Fothergill-Robinson, Julie / Furlan, Giacomo / Ross, Robert L / Limbach, Patrick A / Ramalho-Santos, Miguel

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show ...

    Abstract Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show that m
    Language English
    Publishing date 2023-02-01
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.30.526234
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: m

    Collignon, Evelyne / Cho, Brandon / Furlan, Giacomo / Fothergill-Robinson, Julie / Martin, Sylvia-Bryn / McClymont, Sarah A / Ross, Robert L / Limbach, Patrick A / Ramalho-Santos, Miguel

    Nature cell biology

    2023  Volume 25, Issue 9, Page(s) 1279–1289

    Abstract: Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show ...

    Abstract Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show that N
    MeSH term(s) Animals ; Mice ; Adult Stem Cells ; Blastocyst ; Embryonic Stem Cells ; Methylation ; RNA, Messenger/genetics
    Chemical Substances RNA, Messenger ; N-methyladenosine (CLE6G00625) ; Mettl3 protein, mouse (EC 2.1.1.-)
    Language English
    Publishing date 2023-09-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-023-01212-x
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  4. Book ; Online: Neural disambiguation of lemma and part of speech in morphologically rich languages

    Quecedo, José María Hoya / Koppatz, Maximilian W. / Furlan, Giacomo / Yangarber, Roman

    2020  

    Abstract: We consider the problem of disambiguating the lemma and part of speech of ambiguous words in morphologically rich languages. We propose a method for disambiguating ambiguous words in context, using a large un-annotated corpus of text, and a morphological ...

    Abstract We consider the problem of disambiguating the lemma and part of speech of ambiguous words in morphologically rich languages. We propose a method for disambiguating ambiguous words in context, using a large un-annotated corpus of text, and a morphological analyser -- with no manual disambiguation or data annotation. We assume that the morphological analyser produces multiple analyses for ambiguous words. The idea is to train recurrent neural networks on the output that the morphological analyser produces for unambiguous words. We present performance on POS and lemma disambiguation that reaches or surpasses the state of the art -- including supervised models -- using no manually annotated data. We evaluate the method on several morphologically rich languages.

    Comment: This paper contains corrigenda to a previously published paper (Hoya Quecedo et al., 2020). It corrects a mistake in the original evaluation setup, and the results reported in Section 6., in Tables 5, 6, and 7
    Keywords Computer Science - Computation and Language
    Subject code 410
    Publishing date 2020-07-12
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Embryonic origin and lineage hierarchies of the neural progenitor subtypes building the zebrafish adult midbrain.

    Galant, Sonya / Furlan, Giacomo / Coolen, Marion / Dirian, Lara / Foucher, Isabelle / Bally-Cuif, Laure

    Developmental biology

    2016  Volume 420, Issue 1, Page(s) 120–135

    Abstract: Neurogenesis in the post-embryonic vertebrate brain varies in extent and efficiency between species and brain territories. Distinct neurogenesis modes may account for this diversity, and several neural progenitor subtypes, radial glial cells (RG) and ... ...

    Abstract Neurogenesis in the post-embryonic vertebrate brain varies in extent and efficiency between species and brain territories. Distinct neurogenesis modes may account for this diversity, and several neural progenitor subtypes, radial glial cells (RG) and neuroepithelial progenitors (NE), have been identified in the adult zebrafish brain. The neurogenic sequences issued from these progenitors, and their contribution to brain construction, remain incompletely understood. Here we use genetic tracing techniques based on conditional Cre recombination and Tet-On neuronal birthdating to unravel the neurogenic sequence operating from NE progenitors in the zebrafish post-embryonic optic tectum. We reveal that a subpopulation of her5-positive NE cells of the posterior midbrain layer stands at the top of a neurogenic hierarchy involving, in order, the amplification pool of the tectal proliferation zone (TPZ), followed by her4-positive RG cells with transient neurogenic activity. We further demonstrate that the adult her5-positive NE pool is issued in lineage from an identically located NE pool expressing the same gene in the embryonic neural tube. Finally, we show that these features are reminiscent of the neurogenic sequence and embryonic origin of the her9-positive progenitor NE pool involved in the construction of the lateral pallium at post-embryonic stages. Together, our results highlight the shared recruitment of an identical neurogenic strategy by two remote brain territories, where long-lasting NE pools serve both as a growth zone and as the life-long source of young neurogenic RG cells.
    MeSH term(s) Aging/physiology ; Animals ; Cell Lineage/drug effects ; Doxycycline/pharmacology ; Embryo, Nonmammalian/cytology ; Embryo, Nonmammalian/drug effects ; Embryo, Nonmammalian/metabolism ; Mesencephalon/cytology ; Mesencephalon/drug effects ; Mesencephalon/embryology ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism ; Neuroepithelial Cells/cytology ; Neuroepithelial Cells/drug effects ; Neuroepithelial Cells/metabolism ; Neurogenesis/drug effects ; Neuroglia/cytology ; Neuroglia/drug effects ; Neuroglia/metabolism ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Recombination, Genetic/genetics ; Superior Colliculi/cytology ; Superior Colliculi/drug effects ; Superior Colliculi/embryology ; Superior Colliculi/metabolism ; Tamoxifen/analogs & derivatives ; Tamoxifen/pharmacology ; Zebrafish/embryology
    Chemical Substances Tamoxifen (094ZI81Y45) ; afimoxifene (17197F0KYM) ; Doxycycline (N12000U13O)
    Language English
    Publishing date 2016-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2016.09.022
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  6. Article ; Online: Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling.

    Huyghe, Aurélia / Furlan, Giacomo / Ozmadenci, Duygu / Galonska, Christina / Charlton, Jocelyn / Gaume, Xavier / Combémorel, Noémie / Riemenschneider, Christina / Allègre, Nicolas / Zhang, Jenny / Wajda, Pauline / Rama, Nicolas / Vieugué, Pauline / Durand, Isabelle / Brevet, Marie / Gadot, Nicolas / Imhof, Thomas / Merrill, Bradley J / Koch, Manuel /
    Mehlen, Patrick / Chazaud, Claire / Meissner, Alexander / Lavial, Fabrice

    Nature cell biology

    2020  Volume 22, Issue 4, Page(s) 389–400

    Abstract: In mouse embryonic stem cells (mESCs), chemical blockade of Gsk3α/β and Mek1/2 (2i) instructs a self-renewing ground state whose endogenous inducers are unknown. Here we show that the axon guidance cue Netrin-1 promotes naive pluripotency by triggering ... ...

    Abstract In mouse embryonic stem cells (mESCs), chemical blockade of Gsk3α/β and Mek1/2 (2i) instructs a self-renewing ground state whose endogenous inducers are unknown. Here we show that the axon guidance cue Netrin-1 promotes naive pluripotency by triggering profound signalling, transcriptomic and epigenetic changes in mESCs. Furthermore, we demonstrate that Netrin-1 can substitute for blockade of Gsk3α/β and Mek1/2 to sustain self-renewal of mESCs in combination with leukaemia inhibitory factor and regulates the formation of the mouse pluripotent blastocyst. Mechanistically, we reveal how Netrin-1 and the balance of its receptors Neo1 and Unc5B co-regulate Wnt and MAPK pathways in both mouse and human ESCs. Netrin-1 induces Fak kinase to inactivate Gsk3α/β and stabilize β-catenin while increasing the phosphatase activity of a Ppp2r2c-containing Pp2a complex to reduce Erk1/2 activity. Collectively, this work identifies Netrin-1 as a regulator of pluripotency and reveals that it mediates different effects in mESCs depending on its receptor dosage, opening perspectives for balancing self-renewal and lineage commitment.
    MeSH term(s) Animals ; Cell Line ; Embryo, Mammalian ; Extracellular Signal-Regulated MAP Kinases/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Focal Adhesion Kinase 1/genetics ; Focal Adhesion Kinase 1/metabolism ; Gene Expression Regulation, Developmental ; Glycogen Synthase Kinase 3 beta/antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta/genetics ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Leukemia Inhibitory Factor/genetics ; Leukemia Inhibitory Factor/metabolism ; MAP Kinase Kinase 1/antagonists & inhibitors ; MAP Kinase Kinase 1/genetics ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Kinase 2/antagonists & inhibitors ; MAP Kinase Kinase 2/genetics ; MAP Kinase Kinase 2/metabolism ; Male ; Mice ; Mice, Knockout ; Mice, SCID ; Mouse Embryonic Stem Cells/cytology ; Mouse Embryonic Stem Cells/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Netrin Receptors/genetics ; Netrin Receptors/metabolism ; Netrin-1/genetics ; Netrin-1/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/metabolism ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances CTNNB1 protein, mouse ; Isoenzymes ; Leukemia Inhibitory Factor ; Lif protein, mouse ; NEO1 protein, human ; Nerve Tissue Proteins ; Netrin Receptors ; Ntn1 protein, mouse ; PPP2R2C protein, human ; Receptors, Cell Surface ; UNC5B protein, human ; Unc5b protein, mouse ; beta Catenin ; Netrin-1 (158651-98-0) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; Ptk2 protein, mouse (EC 2.7.10.2) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, mouse (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; MAP Kinase Kinase 2 (EC 2.7.12.2) ; Map2k1 protein, mouse (EC 2.7.12.2) ; Map2k2 protein, mouse (EC 2.7.12.2) ; Protein Phosphatase 2 (EC 3.1.3.16)
    Language English
    Publishing date 2020-03-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-020-0483-2
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  7. Article ; Online: Life-Long Neurogenic Activity of Individual Neural Stem Cells and Continuous Growth Establish an Outside-In Architecture in the Teleost Pallium.

    Furlan, Giacomo / Cuccioli, Valentina / Vuillemin, Nelly / Dirian, Lara / Muntasell, Anna Janue / Coolen, Marion / Dray, Nicolas / Bedu, Sébastien / Houart, Corinne / Beaurepaire, Emmanuel / Foucher, Isabelle / Bally-Cuif, Laure

    Current biology : CB

    2017  Volume 27, Issue 21, Page(s) 3288–3301.e3

    Abstract: Spatiotemporal variations of neurogenesis are thought to account for the evolution of brain shape. In the dorsal telencephalon (pallium) of vertebrates, it remains unresolved which ancestral neurogenesis mode prefigures the highly divergent ... ...

    Abstract Spatiotemporal variations of neurogenesis are thought to account for the evolution of brain shape. In the dorsal telencephalon (pallium) of vertebrates, it remains unresolved which ancestral neurogenesis mode prefigures the highly divergent cytoarchitectures that are seen in extant species. To gain insight into this question, we developed genetic tools to generate here the first 4-dimensional (3D + birthdating time) map of pallium construction in the adult teleost zebrafish. Using a Tet-On-based genetic birthdating strategy, we identify a "sequential stacking" construction mode where neurons derived from the zebrafish pallial germinal zone arrange in outside-in, age-related layers from a central core generated during embryogenesis. We obtained no evidence for overt radial or tangential neuronal migrations. Cre-lox-mediated tracing, which included following Brainbow clones, further demonstrates that this process is sustained by the persistent neurogenic activity of individual pallial neural stem cells (NSCs) from embryo to adult. Together, these data demonstrate that the spatiotemporal control of NSC activity is an important driver of the macroarchitecture of the zebrafish adult pallium. This simple mode of pallium construction shares distinct traits with pallial genesis in mammals and non-mammalian amniotes such as birds or reptiles, suggesting that it may exemplify the basal layout from which vertebrate pallial architectures were elaborated.
    MeSH term(s) Animals ; Biomarkers/metabolism ; Neocortex/embryology ; Neural Stem Cells/cytology ; Neurogenesis/physiology ; Telencephalon/anatomy & histology ; Telencephalon/cytology ; Zebrafish/anatomy & histology ; Zebrafish/embryology
    Chemical Substances Biomarkers
    Language English
    Publishing date 2017-10-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2017.09.052
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