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5. FRUIT BATS AS NATURAL RESERVOIR OF HIGHLY PATHOGENIC HENIPAVIRUSES: HIGH PERMISSIVENESS OF REPROGRAMMED PTEROPUS BAT CELLS

Author

Horvat, Branka, Aurine, Noémie, Gaudino, Maria, Fouret, Julien, Baquerre, Camille, Jean, Christian, Reynard, Olivier, Dumont, Claire, Rival-Gervier, Sylvie, Montillet, Guillaume, Kress, Clemences, Georges-Courbot, Marie-Claude, Legras-Lachuer, Catherine, Pain, Bertrand, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ViroScan3D SAS [Trévoux, France], Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, and Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Bats are asymptomatic hosts for numerous viruses, including highly pathogenic zoonotic henipaviruses, Nipah (NiV) and Hendra. Understanding of how bats control viral infection requires better characterization of bat-derived viruses and development of relevant permissive cellular models. We analysed NiV isolate obtained from a Pteropus lylei bat in Cambodia in 2003 (CSUR381), where human outbreaks of NiV infection have not been detected so far. Full-genome sequencing and phylogenetic analyses confirmed that CSUR381 is part of the NiV-Malaysia genotype. Cell permissiveness was similar in both bat and human cell lines and replication of CSUR381 was alike to other two NiV isolates. In the hamster animal model CSUR381 induced lethal infection. These data suggest that the Cambodia batderived NiV isolate has high pathogenic potential, providing an insight for better risk assessment for future NiV outbreaks in Southeast Asia. Most of the available bat cells are immortalized lines, significantly impacting the overall cell response that may alter the virus-cell interactions. Therefore, by applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2 and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting neural stem cell-like characteristics. These cells present a unique interferon-stimulated transcriptomic signature but still produce and respond to IFN type I. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, even more than Vero cells, commonly used for virus isolation. Future direct reprogramming of bat primary cells into various differentiated cell types should facilitate the isolation of new bat viruses and further studies of virus-bat interaction, towards better understating of the efficient bat anti-viral response.

Published
2022

6. Reprogrammed Pteropus Bat Stem Cells as A Model to Study Host-Pathogen Interaction during Henipavirus Infection

Author

Aurine, Noémie, Baquerre, Camille, Gaudino, Maria, Jean, Christian, Dumont, Claire, Rival-Gervier, Sylvie, Kress, Clémence, Horvat, Branka, Pain, Bertrand, PAIN, Bertrand, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Structure et fonctions de la protéine C du virus Nipah - - NiPah-C2018 - ANR-18-CE11-0014 - AAPG2018 - VALID, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The study was supported by LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007), operated by the French National Research Agency (ANR), and by ANR-18-CE11-0014, by grants from the 'Finovi Foundation' (AO13) and Aviesan Sino-French agreement on Nipah virus study., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), ANR-18-CE11-0014,NiPah-C,Structure et fonctions de la protéine C du virus Nipah(2018), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The study was supported by LABEX ECOFECT (ANR-11-LABX-0048) of Lyon University, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007), operated by the French National Research Agency (ANR), and by ANR-18-CE11-0014-02, by grants from the 'Finovi Foundation' (AO13) and Aviesan Sino-French agreement on Nipah virus study., and Rival-Gervier, Sylvie

Subjects
[SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV]Life Sciences [q-bio], Henipavirus, bats, interferon-stimulated gene, reprogramming, Nipah virus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, [SDV] Life Sciences [q-bio], stem cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biology (General), emerging infection, innate immunity, transcriptome, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract

The data sets are available in GSE134585 datasets.; International audience; Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a combination of ESRRB (Estrogen Related Receptor Beta), CDX2 (Caudal type Homeobox 2), and c-MYC (MYC proto-oncogene) transcription factors, we generated bat reprogrammed cells. These cells exhibit stem cell-like characteristics and neural stem cell molecular signature. In contrast to primary fibroblastic cells, these reprogrammed stem cells are highly permissive to henipaviruses and exhibit specific transcriptomic profiles with the particular expression of certain susceptibility factors such as interferon-stimulated genes (ISG), which may be related to viral infection. These Pteropus bat reprogrammed stem cells should represent an important experimental tool to decipher interactions during henipaviruses infection in Pteropus bats, facilitate isolation and production of bat-borne viruses, and to better understand the bat biology.

Published
2021

7. Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy

Author

Lentini, Célia, primary, d’Orange, Marie, additional, Marichal, Nicolás, additional, Trottmann, Marie-Madeleine, additional, Vignoles, Rory, additional, Foucault, Louis, additional, Verrier, Charlotte, additional, Massera, Céline, additional, Raineteau, Olivier, additional, Conzelmann, Karl-Klaus, additional, Rival-Gervier, Sylvie, additional, Depaulis, Antoine, additional, Berninger, Benedikt, additional, and Heinrich, Christophe, additional

Published
2021
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11. Transcriptional dysregulation in postnatal glutamatergic progenitors contributes to closure of thecortical neurogenic period

Author

Marcy, Guillaume, Lo Giudice, Quentin, Zweifel, Stefan, Angonin, Diane, Fiorelli, Roberto, Abrous, Djoher Nora, Rival-Gervier, Sylvie, Koehl, Muriel, Jabaudon, Denis, Donega, Vanessa, and Raineteau, Olivier

Subjects
Bcl11a, canonical Wnt pathway, epitranscriptome, fate mapping, glutamatergic progenitors, postnatal neurogenesis, single cell transcriptomics
Published
2018

12. Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period

Author

Donega, Vanessa, Marcy, Guillaume, Lo Giudice, Quentin, Zweifel, Stefan, Angonin, Diane, Fiorelli, Roberto, Abrous, Djoher Nora, Rival-Gervier, Sylvie, Koehl, Muriel, Jabaudon, Denis, Raineteau, Olivier, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Brain Research Institute [Zurich, Suisse], University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Koehl, Muriel, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE), Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Programme Avenir Lyon Saint-Etienne, FRC ('Federation pour la Recherche sur le Cerveau'), Labex Cortex, IRME ('Institut pour la Recherche sur la Moelle epiniere et l'Encephale'), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)-Universität Zürich [Zürich] = University of Zurich (UZH)

Subjects
Retinal Ganglion Cells, Transcription, Genetic, Neurogenesis, Mice, Transgenic, Nerve Tissue Proteins, single cell transcriptomics, Glutamates, Neural Stem Cells, epitranscriptome, Cell Movement, Lateral Ventricles, Basic Helix-Loop-Helix Transcription Factors, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], canonical Wnt pathway, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, Bcl11a, glutamatergic progenitors, Gene Expression Regulation, Developmental, Cell Differentiation, postnatal neurogenesis, ddc:616.8, Animals, Newborn, lcsh:Biology (General), fate mapping, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Single-Cell Analysis
Abstract

Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal radial glial cells that persist after birth in the dorsal subventricular zone and continue to give rise to cortical neurons, although with low efficiency. Single-cell RNA sequencing reveals a dysregulation of transcriptional programs, which parallels changes in m6A methylation and correlates with the gradual decline in cortical neurogenesis observed in vivo. Rescuing experiments show that postnatal progenitors are partially permissive to genetic and pharmacological manipulations. Our study provides an in-depth characterization of postnatal Glu progenitors and identifies potential therapeutic targets for promoting brain repair., Cell Reports, 22 (10), ISSN:2666-3864, ISSN:2211-1247

Published
2018

13. Discriminate alternative pluripotency states by means of Endogenous Retroviral Elements

Author

Rival-Gervier, Sylvie, Roman, Tarjimanov, Roberge, Alexis, Dhayer, Mélanie, Montillet, Guillaume, Christian, Jean, Beaujean, Nathalie, Pain, Bertrand, Beaujean, Nathalie, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

19. The D4Z4 insulator protects retrovirus transgenes from silencing in pluripotent stem cells

Author

Rival-Gervier, Sylvie, Barsyte-Lovejoy, Dalia, Lo, Mandy, Anderson, Susan, Pasceri, Peter, Jin, Jian, Arrowsmith, Cheryl H., Ellis, James, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), University of Toronto, Structural Genomics Consortium, University of North Carolina, Epigenetics. CAN., International Society of Stem Cell Research (ISSCR). INT., and ProdInra, Migration

Subjects
d4z4, [SDV.BDD] Life Sciences [q-bio]/Development Biology, isolant, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

22. Erratum: A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells

Author

Vedadi, Masoud, primary, Barsyte-Lovejoy, Dalia, additional, Liu, Feng, additional, Rival-Gervier, Sylvie, additional, Allali-Hassani, Abdellah, additional, Labrie, Viviane, additional, Wigle, Tim J, additional, DiMaggio, Peter A, additional, Wasney, Gregory A, additional, Siarheyeva, Alena, additional, Dong, Aiping, additional, Tempel, Wolfram, additional, Wang, Sun-Chong, additional, Chen, Xin, additional, Chau, Irene, additional, Mangano, Thomas J, additional, Huang, Xi-ping, additional, Simpson, Catherine D, additional, Pattenden, Samantha G, additional, Norris, Jacqueline L, additional, Kireev, Dmitri B, additional, Tripathy, Ashutosh, additional, Edwards, Aled, additional, Roth, Bryan L, additional, Janzen, William P, additional, Garcia, Benjamin A, additional, Petronis, Arturas, additional, Ellis, James, additional, Brown, Peter J, additional, Frye, Stephen V, additional, Arrowsmith, Cheryl H, additional, and Jin, Jian, additional

Published
2011
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23. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells

Author

Vedadi, Masoud, primary, Barsyte-Lovejoy, Dalia, additional, Liu, Feng, additional, Rival-Gervier, Sylvie, additional, Allali-Hassani, Abdellah, additional, Labrie, Viviane, additional, Wigle, Tim J, additional, DiMaggio, Peter A, additional, Wasney, Gregory A, additional, Siarheyeva, Alena, additional, Dong, Aiping, additional, Tempel, Wolfram, additional, Wang, Sun-Chong, additional, Chen, Xin, additional, Chau, Irene, additional, Mangano, Thomas J, additional, Huang, Xi-ping, additional, Simpson, Catherine D, additional, Pattenden, Samantha G, additional, Norris, Jacqueline L, additional, Kireev, Dmitri B, additional, Tripathy, Ashutosh, additional, Edwards, Aled, additional, Roth, Bryan L, additional, Janzen, William P, additional, Garcia, Benjamin A, additional, Petronis, Arturas, additional, Ellis, James, additional, Brown, Peter J, additional, Frye, Stephen V, additional, Arrowsmith, Cheryl H, additional, and Jin, Jian, additional

Published
2011
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32. The D4Z4 Macrosatellite Repeat Acts as a CTCF and AType Lamins-Dependent Insulator in Facio-Scapulo- Humeral Dystrophy.

Author

Ottaviani, Alexandre, Rival-Gervier, Sylvie, Boussouar, Amina, Foerster, Andrea M., Rondier, Delphine, Sacconi, Sabrina, Desnuelle, Claude, Gilson, Eric, and Magdinier, Frédérique

Subjects
*DYSTROPHY, *HUMAN genome, *MYOBLASTS, *CELLS, *PATIENTS
Abstract

Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD), which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s) through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer-promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients. [ABSTRACT FROM AUTHOR]

Published
2009
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33. The Insulator Effect of the 5′HS4 Region from the β-globin Chicken Locus on the Rabbit WAPGene Promoter Activity in Transgenic Mice

Author

Rival-Gervier, Sylvie, Pantano, Thais, Viglietta, Céline, Maeder, Caroline, Prince, Sonia, Attal, Joe, Jolivet, Geneviève, and Houdebine, Louis-Marie

Abstract

Previous studies have shown that the 5′HS4 DNaseI hypersensitive site of the chicken β-globin locus is endowed with classic insulator activities: (i) it blocks the interaction between promoter and enhancers when it is inserted between them (ii) it confers expression of integrated foreign genes independent of their position in the chromatin. The aim of this present work was to determine whether the 5′HS4 element was able to stimulate the expression level and/or to increase the expression frequency of a luc+ reporter gene controlled by the rabbit WAPgene promoter. Two constructs with 5′HS4 insulator (p5′HS4-WAPluc) or without (pWAPluc) were introduced in mouse fertilised oocytes. All transgenic lines containing the 5′HS4 element (six lines) expressed the transgene whereas only two out of eight lines harbouring the pWAP-luc construct expressed the transgene to a significant level. Moreover, the mean level of expression was seven times higher in p5′HS4WAP-luc lines than in pWAP-luc lines. Even all these benefits on transgene expression, the 5′HS4 element did not confer a copy-dependent expression, did not decrease the ectopic expression of the reporter gene and did not decrease the variability of expression. Thus, the 5′HS4 element does not have all the properties of a perfect insulator on a construct containing the luc+ reporter gene controlled by the rabbit WAPpromoter.

Published
2003
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34. Reprogrammed Pteropus Bat Stem Cells Present Distinct Immune Signature and are Highly Permissive for Henipaviruses

Author

Camille Baquerre, Maria Gaudino, Bertrand Pain, Clémence Kress, Christian Jean, Claire Dumont, Branka Horvat, Noémie Aurine, Sylvie Rival-Gervier, Immunobiologie des infections virales – Immunobiology of Viral Infections (IbIV), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Institut cellule souche et cerveau (SBRI), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut universitaire de formation des maîtres - Centre Val de Loire (IUFM Centre Val-de-Loire), Université d'Orléans (UO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité mixte de recherche biologie moléculaire de la cellule, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Rival-Gervier, Sylvie, and École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
animal structures, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Somatic cell, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Immune system, Interferon, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, Genetics, 0303 health sciences, biology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, biology.organism_classification, Pteropus, 3. Good health, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV] Life Sciences [q-bio], Stem cell, Reprogramming, 030217 neurology & neurosurgery, Henipavirus, medicine.drug
Abstract

Bats are unique among mammals due to the ability of powered flight and exceptional longevity. They are also asymptomatic hosts for numerous viruses, including recently emerged zoonotic Henipaviruses Nipah and Hendra, which are highly pathogenic for humans and other mammals. Better understanding of how bats control viral infection requires development of relevant permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2, and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting stem cell-like characteristics and a neural stem cell-like molecular signature. These cells present a unique interferon-stimulated transcriptomic signature and both produce and respond to interferon type-I, highlighting differences between stem cells from bats and other mammals. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, thereby enabling isolation of new bat viruses, study of virus-bat interactions, and better understanding of bat biology.Summary sentenceSomatic reprogramming provides new bat stem cells with unique immune properties and original viral permissivness

Published
2020

35. NANOG Is Required for the Long-Term Establishment of Avian Somatic Reprogrammed Cells

Author

Sylvie Rival-Gervier, Bertrand Pain, Clémence Kress, Pauline Aubel, Guillaume Montillet, Aurélie Fuet, Christian Jean, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR [AviRepro - ANR 09-BLAN-0141], [CRB-ANIM - ANR-11-INBS-0003], ECLAIRE [ANR-14-CE16-0002-01], Université Claude Bernard Lyon 1 (UCBL), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génomique et Physiologie de la Lactation (GPL), Institut National de la Recherche Agronomique (INRA), Unité mixte de recherche biologie moléculaire de la cellule, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Rival-Gervier, Sylvie, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
0301 basic medicine, Telomerase, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, duck, Somatic cell, [SDV]Life Sciences [q-bio], avian species, LIN28, Biochemistry, blastoderm, 0302 clinical medicine, [SDV.BDD]Life Sciences [q-bio]/Development Biology, NANOG, chicken, embryonic stem cells, embryos, phylogenic comparison, pluripotency, somatic reprogramming, lcsh:QH301-705.5, lcsh:R5-920, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, blastoderme, Nanog Homeobox Protein, Cellular Reprogramming, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], Ducks, KLF4, embryonic structures, lcsh:Medicine (General), Reprogramming, Homeobox protein NANOG, cellule souche embryonnaire, animal structures, Induced Pluripotent Stem Cells, poulet, Biology, Article, 03 medical and health sciences, SOX2, phylogénie, Genetics, Animals, pluripotence, canard, Cell Proliferation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, Embryonic stem cell, Clone Cells, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, lcsh:Biology (General), Chickens, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Summary Somatic reprogramming, which was first identified in rodents, remains poorly described in non-mammalian species. Here, we generated avian reprogrammed cells by reprogramming of chicken and duck primary embryonic fibroblasts. The efficient generation of long-term proliferating cells depends on the method of delivery of reprogramming factors and the addition of NANOG and LIN28 to the canonical OCT4, SOX2, KLF4, and c-MYC gene combination. The reprogrammed cells were positive for several key pluripotency-associated markers including alkaline phosphatase activity, telomerase activity, SSEA1 expression, and specific cell cycle and epigenetic markers. Upregulated endogenous pluripotency-associated genes included POU5F3 (POUV) and KLF4, whereas cells failed to upregulate NANOG and LIN28A. However, cells showed a tumorigenic propensity when injected into recipient embryos. In conclusion, although the somatic reprogramming process is active in avian primary cells, it needs to be optimized to obtain fully reprogrammed cells with similar properties to those of chicken embryonic stem cells., Highlights • NANOG is required for avian somatic reprogramming • NANOG is necessary for long-term establishment of avian reprogrammed cells • Avian reprogrammed cells express pluripotency markers • Avian cells are only partially reprogrammed, In this article, the authors show that the NANOG gene plays a crucial role in the long-term establishment of avian reprogrammed cells that have some of the specific markers of stem cells but that do not present all the developmental properties of induced pluripotent stem cells such as described in mammals.

Published
2018

36. Reprogrammed Pteropus Bat Stem Cells as A Model to Study Host-Pathogen Interaction during Henipavirus Infection.

Author

Aurine N, Baquerre C, Gaudino M, Jean C, Dumont C, Rival-Gervier S, Kress C, Horvat B, and Pain B

Abstract

Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a combination of ESRRB (Estrogen Related Receptor Beta), CDX2 (Caudal type Homeobox 2), and c-MYC (MYC proto-oncogene) transcription factors, we generated bat reprogrammed cells. These cells exhibit stem cell-like characteristics and neural stem cell molecular signature. In contrast to primary fibroblastic cells, these reprogrammed stem cells are highly permissive to henipaviruses and exhibit specific transcriptomic profiles with the particular expression of certain susceptibility factors such as interferon-stimulated genes (ISG), which may be related to viral infection. These Pteropus bat reprogrammed stem cells should represent an important experimental tool to decipher interactions during henipaviruses infection in Pteropus bats, facilitate isolation and production of bat-borne viruses, and to better understand the bat biology.

Published
2021
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37. Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period.

Author

Donega V, Marcy G, Lo Giudice Q, Zweifel S, Angonin D, Fiorelli R, Abrous DN, Rival-Gervier S, Koehl M, Jabaudon D, and Raineteau O

Subjects
Animals, Animals, Newborn, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Differentiation, Cell Movement, Lateral Ventricles cytology, Mice, Transgenic, Nerve Tissue Proteins metabolism, Retinal Ganglion Cells cytology, Single-Cell Analysis, Cerebral Cortex cytology, Gene Expression Regulation, Developmental, Glutamates metabolism, Neural Stem Cells cytology, Neural Stem Cells metabolism, Neurogenesis, Transcription, Genetic
Abstract

Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal radial glial cells that persist after birth in the dorsal subventricular zone and continue to give rise to cortical neurons, although with low efficiency. Single-cell RNA sequencing reveals a dysregulation of transcriptional programs, which parallels changes in m 6 A methylation and correlates with the gradual decline in cortical neurogenesis observed in vivo. Rescuing experiments show that postnatal progenitors are partially permissive to genetic and pharmacological manipulations. Our study provides an in-depth characterization of postnatal Glu progenitors and identifies potential therapeutic targets for promoting brain repair., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2018
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38. In vitro and in vivo effects of a multimerized alphas 1-casein enhancer on whey acidic protein gene promoter activity.

Author

Pantano T, Rival-Gervier S, Prince S, Menck-Le Bourhis C, Maeder C, Viglietta C, Houdebine LM, and Jolivet G

Subjects
Animals, Caseins chemistry, Caseins metabolism, Luciferases genetics, Luciferases metabolism, Macromolecular Substances, Mice, Mice, Transgenic, Rabbits, Recombinant Fusion Proteins metabolism, Recombinant Proteins metabolism, Transfection, Whey Proteins, Caseins genetics, Enhancer Elements, Genetic genetics, Milk Proteins genetics, Promoter Regions, Genetic
Abstract

Experimental data obtained in previous works have led to postulate that enhancers increase the frequency of action of a linked promoter in a given cell and may have some insulating effects. The multimerized rabbit alpha s1-casein gene enhancer, the 6i multimer, was added upstream of the rabbit whey acidic protein gene (WAP) promoter (-6,300; +28 bp) fused to the firefly luciferase (luc) gene (6i WAP-luc construct). The 6i multimer increased reporter gene expression in mouse mammary HC11 cells. In transgenic mice, a very weak but significant increase was also observed. More noticeable, no silent lines were found when the 6i multimer was associated to the WAP-luc construct. This reflects the fact that the 6i multimer tends to prevent the silencing of the WAP-luc construct. After addition of the 5'HS4 insulator region from the chicken beta-globin locus upstream of the 6i multimer, similar luciferase levels were measured in 6i WAP-luc and 5'HS4 WAP-luc transgenic mice. Our present data and previous ones, which show that the 6i multimer has no insulating activity on a TK gene promoter construct indicate that the insulating activity of the 6i multimer is construct-dependent and not amplified by the 5'HS4 insulator., (Copyright 2003 Wiley-Liss, Inc.)

Published
2003
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