4 results on '"Sophie Foulon"'
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2. The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands.
- Author
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Sebastian Hutchinson, Sophie Foulon, Aline Crouzols, Roberta Menafra, Brice Rotureau, Andrew D Griffiths, and Philippe Bastin
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The long and complex Trypanosoma brucei development in the tsetse fly vector culminates when parasites gain mammalian infectivity in the salivary glands. A key step in this process is the establishment of monoallelic variant surface glycoprotein (VSG) expression and the formation of the VSG coat. The establishment of VSG monoallelic expression is complex and poorly understood, due to the multiple parasite stages present in the salivary glands. Therefore, we sought to further our understanding of this phenomenon by performing single-cell RNA-sequencing (scRNA-seq) on these trypanosome populations. We were able to capture the developmental program of trypanosomes in the salivary glands, identifying populations of epimastigote, gamete, pre-metacyclic and metacyclic cells. Our results show that parasite metabolism is dramatically remodeled during development in the salivary glands, with a shift in transcript abundance from tricarboxylic acid metabolism to glycolytic metabolism. Analysis of VSG gene expression in pre-metacyclic and metacyclic cells revealed a dynamic VSG gene activation program. Strikingly, we found that pre-metacyclic cells contain transcripts from multiple VSG genes, which resolves to singular VSG gene expression in mature metacyclic cells. Single molecule RNA fluorescence in situ hybridisation (smRNA-FISH) of VSG gene expression following in vitro metacyclogenesis confirmed this finding. Our data demonstrate that multiple VSG genes are transcribed before a single gene is chosen. We propose a transcriptional race model governs the initiation of monoallelic expression.
- Published
- 2021
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3. H3K27me3 is a determinant of chemotolerance in triple-negative breast cancer
- Author
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Sylvain Baulande, Adeline Durand, Anne-Marie Lyne, Almut S Eisele, Pacôme Prompsy, Camille Landragin, Justine Marsolier, Ahmed Dahmani, Céline Vallot, Kevin Grosselin, Sophie Foulon, Amandine Trouchet, Sabrina Tenreira Bento, Elisabetta Marangoni, Leïla Perié, Mylène Bohec, Laura Sourd, Eric Letouzé, Léa Baudre, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), and Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0303 health sciences ,biology ,[SDV]Life Sciences [q-bio] ,Cell fate determination ,medicine.disease ,3. Good health ,Chromatin ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Histone ,Breast cancer ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,medicine ,H3K4me3 ,Triple-negative breast cancer ,030304 developmental biology - Abstract
SummaryTriple-negative breast cancer is associated with the worst prognosis and the highest risk of recurrence among all breast cancer subtypes1. Residual disease, formed by cancer cells persistent to chemotherapy, remains one of the major clinical challenges towards full cure2,3. There is now consensus that non-genetic processes contribute to chemoresistance in various tumor types, notably through the initial emergence of a reversible chemotolerant state4–6. Understanding non-genetic tumor evolution stands now as a prerequisite for the design of relevant combinatorial approaches to delay recurrence. Here we show that the repressive histone mark H3K27me3 is a determinant of cell fate under chemotherapy exposure, monitoring epigenomes, transcriptomes and lineage with single-cell resolution. We identify a reservoir of persister basal cells with EMT markers and activated TGF-β pathway leading to multiple chemoresistance phenotypes. We demonstrate that, in unchallenged cells, H3K27 methylation is a lock to the expression program of persister cells. Promoters are primed with both H3K4me3 and H3K27me3, and removing H3K27me3 is sufficient for their transcriptional activation. Leveraging lineage barcoding, we show that depleting H3K27me3 alters tumor cell fate under chemotherapy insult – a wider variety of tumor cells tolerate chemotherapy. Our results highlight how chromatin landscapes shape the potential of unchallenged cancer cells to respond to therapeutic stress.
- Published
- 2021
4. The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands
- Author
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Brice Rotureau, Sophie Foulon, Andrew D. Griffiths, Roberta Menafra, Philippe Bastin, Aline Crouzols, Sebastian Hutchinson, Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This project has received funding from the European Union’s (https://ec.europa.eu/) Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 794979 to S.H. S.H. was funded by a European Union Marie Skłodowska-Curie (No 794979) and an Institut Pasteur (https://www.pasteur.fr/) Roux-Cantarini fellowship. Funding was provided by the Institut Pasteur, and the French Government Agence Nationale de la Recherche (https://anr.fr/) Investissement d’Avenir Programme—Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) to P.B. This work has received the support of 'Institut Pierre-Gilles de Gennes' (laboratoire d’excellence, 'Investissements d’avenir' program ANR-10-IDEX-0001-02 PSL, ANR-10-LABX-31 and ANR-10-EQPX-34. R.M. was supported by the Agence Nationale de la Recherche project 'Cellectchip' ANR-14-CE10-0013 to A.D.G. ICGex Next Generation Sequencing platform of the Institut Curie supported by the grants ANR-10-EQPX-03 (Equipex) and ANR-10-INBS-09-08 (France Génomique Consortium) from the Agence Nationale de la Recherche ('Investissements d’Avenir' program), by the Canceropole Ile-de-France and by the Site de Recherche Intégrée sur le Cancer (https://siric.curie.fr/) - Curie program - SiRIC Grant INCa-DGOS- 4654., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-LABX-0031,IPGG_LABEX,Pierre-Gilles de Gennes Institute for microfluidics(2010), ANR-10-EQPX-0034,IPGG,Institut Pierre Gilles de Gennes pour la microfluidique(2010), ANR-14-CE10-0013,CELLECTCHIP,ANALYSE DE LA DYNAMIQUE DE MARQUES EPIGENETIQUES PAR CHIP-SEQ SUR CELLULES INDIVIDUELLES AU COURS DE LA PHASE S ET DE L'EMBRYOGENESE CHEZ DES MAMMIFERES(2014), ANR-10-EQPX-0003,ICGex,Equipement de biologie intégrative du cancer pour une médecine personnalisée(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 794979,H2020-MSCA-IF-2017,scTRYPseq(2019), Rotureau, Brice, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Pierre-Gilles de Gennes Institute for microfluidics - - IPGG_LABEX2010 - ANR-10-LABX-0031 - LABX - VALID, Equipements d'excellence - Institut Pierre Gilles de Gennes pour la microfluidique - - IPGG2010 - ANR-10-EQPX-0034 - EQPX - VALID, Appel à projets générique - ANALYSE DE LA DYNAMIQUE DE MARQUES EPIGENETIQUES PAR CHIP-SEQ SUR CELLULES INDIVIDUELLES AU COURS DE LA PHASE S ET DE L'EMBRYOGENESE CHEZ DES MAMMIFERES - - CELLECTCHIP2014 - ANR-14-CE10-0013 - Appel à projets générique - VALID, Equipements d'excellence - Equipement de biologie intégrative du cancer pour une médecine personnalisée - - ICGex2010 - ANR-10-EQPX-0003 - EQPX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, and Understanding the initiation virulence gene expression in African trypanosomes - scTRYPseq - - H2020-MSCA-IF-20172019-04-01 - 2021-03-31 - 794979 - VALID
- Subjects
Life Cycles ,[SDV]Life Sciences [q-bio] ,Cell ,Gene Expression ,RNA-Seq ,Protozoology ,Salivary Glands ,Database and Informatics Methods ,Medical Conditions ,0302 clinical medicine ,Gene expression ,Medicine and Health Sciences ,MESH: Animals ,Biology (General) ,MESH: Tsetse Flies ,Protozoans ,chemistry.chemical_classification ,Regulation of gene expression ,0303 health sciences ,biology ,Eukaryota ,Genomics ,MESH: Gene Expression Regulation ,Cell biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Epimastigotes ,Protozoan Life Cycles ,Anatomy ,Transcriptome Analysis ,Sequence Analysis ,Variant Surface Glycoproteins, Trypanosoma ,Research Article ,MESH: Salivary Glands ,Trypanosoma ,Tsetse Flies ,Bioinformatics ,QH301-705.5 ,Trypanosoma brucei brucei ,MESH: Insect Vectors ,Trypanosoma brucei ,Research and Analysis Methods ,Microbiology ,03 medical and health sciences ,Exocrine Glands ,parasitic diseases ,Genetics ,Parasitic Diseases ,Trypanosoma Brucei ,medicine ,Animals ,MESH: RNA-Seq ,Gene ,030304 developmental biology ,Organisms ,MESH: Trypanosoma brucei brucei ,Biology and Life Sciences ,Computational Biology ,RNA ,RC581-607 ,Genome Analysis ,biology.organism_classification ,Parasitic Protozoans ,Insect Vectors ,Gene Expression Regulation ,chemistry ,MESH: Variant Surface Glycoproteins, Trypanosoma ,Immunologic diseases. Allergy ,Glycoprotein ,Digestive System ,Sequence Alignment ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The long and complex Trypanosoma brucei development in the tsetse fly vector culminates when parasites gain mammalian infectivity in the salivary glands. A key step in this process is the establishment of monoallelic variant surface glycoprotein (VSG) expression and the formation of the VSG coat. The establishment of VSG monoallelic expression is complex and poorly understood, due to the multiple parasite stages present in the salivary glands. Therefore, we sought to further our understanding of this phenomenon by performing single-cell RNA-sequencing (scRNA-seq) on these trypanosome populations. We were able to capture the developmental program of trypanosomes in the salivary glands, identifying populations of epimastigote, gamete, pre-metacyclic and metacyclic cells. Our results show that parasite metabolism is dramatically remodeled during development in the salivary glands, with a shift in transcript abundance from tricarboxylic acid metabolism to glycolytic metabolism. Analysis of VSG gene expression in pre-metacyclic and metacyclic cells revealed a dynamic VSG gene activation program. Strikingly, we found that pre-metacyclic cells contain transcripts from multiple VSG genes, which resolves to singular VSG gene expression in mature metacyclic cells. Single molecule RNA fluorescence in situ hybridisation (smRNA-FISH) of VSG gene expression following in vitro metacyclogenesis confirmed this finding. Our data demonstrate that multiple VSG genes are transcribed before a single gene is chosen. We propose a transcriptional race model governs the initiation of monoallelic expression., Author summary African trypanosomes are parasitic protists which cause endemic disease in sub-Saharan Africa. To evade mammalian immune responses the parasite has developed a system of antigenic variation, where the surface of the cell is covered in a tightly packed coat of variant surface glycoproteins (VSGs). Each cell expresses only one variant surface glycoprotein at a time, and this is periodically switched to evade new antibodies. The process of singular gene expression is termed monoallelic expression and this has two components, establishment and maintenance, i.e. how a single gene is selected for expression and how its singular expression is maintained throughout successive generations. The establishment of monoallelic VSG gene expression occurs in the salivary gland of the tsetse fly vector, although this process is not well understood. We used single cell gene expression profiling applied to thousands of single cells in the salivary gland of the fly. We show that in order to select a single gene, trypanosomes initially transcribe multiple VSGs before a single gene is selected for high-level expression. We propose a model where this process is driven by a race to accumulate transcription factors at a single VSG gene.
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